rs121918007

Variant names:

• chr1-21564139-G-A
• rs121918007
• NM_000478.6:c.571G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-21564139-G-A
• chr1-21564139-G-C
• chr1-21564139-G-T

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 12P and 1B. PM1 PM5 PP5_Very_Strong BP4

The NM_000478.6(ALPL):​c.571G>A​(p.Glu191Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00141 in 1,614,074 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E191G) has been classified as Likely pathogenic.

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (9 hom.)
• Consequence: ALPL NM_000478.6 missense
• Clinical Significance: Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:39 O:1
• Conservation: PhyloP100: 4.64

Genes affected

ALPL (HGNC:438): (alkaline phosphatase, biomineralization associated) This gene encodes a member of the alkaline phosphatase family of proteins. There are at least four distinct but related alkaline phosphatases: intestinal, placental, placental-like, and liver/bone/kidney (tissue non-specific). The first three are located together on chromosome 2, while the tissue non-specific form is located on chromosome 1. The product of this gene is a membrane bound glycosylated enzyme that is not expressed in any particular tissue and is, therefore, referred to as the tissue-nonspecific form of the enzyme. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature enzyme. This enzyme may play a role in bone mineralization. Mutations in this gene have been linked to hypophosphatasia, a disorder that is characterized by hypercalcemia and skeletal defects. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PM1: In a hotspot region, there are 5 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 9 uncertain in NM_000478.6
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr1-21564140-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1455023.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• PP5: Variant 1-21564139-G-A is Pathogenic according to our data. Variant chr1-21564139-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 13670.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-21564139-G-A is described in Lovd as [Pathogenic]. Variant chr1-21564139-G-A is described in Lovd as [Likely_pathogenic]. Variant chr1-21564139-G-A is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.014826685). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALPL	NM_000478.6	c.571G>A	p.Glu191Lys	missense_variant	Exon 6 of 12	ENST00000374840.8	NP_000469.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALPL	ENST00000374840.8	c.571G>A	p.Glu191Lys	missense_variant	Exon 6 of 12	1	NM_000478.6	ENSP00000363973.3

Frequencies

GnomAD3 genomes AF: 0.00187 AC: 285 AN: 152160 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0170

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00138

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00244 AC: 613 AN: 251204 Hom.: 4 AF XY: 0.00254 AC XY: 345 AN XY: 135818

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0171

Gnomad NFE exome AF: 0.00202

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00137 AC: 1996 AN: 1461796 Hom.: 9 Cov.: 32 AF XY: 0.00134 AC XY: 976 AN XY: 727204

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.0163

Gnomad4 NFE exome AF: 0.000922

Gnomad4 OTH exome AF: 0.00151

GnomAD4 genome AF: 0.00187 AC: 285 AN: 152278 Hom.: 1 Cov.: 32 AF XY: 0.00255 AC XY: 190 AN XY: 74458

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0170

Gnomad4 NFE AF: 0.00138

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000991 Hom.: 1

Bravo AF: 0.000578

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00128 AC: 11

ExAC AF: 0.00257 AC: 312

EpiCase AF: 0.00109

EpiControl AF: 0.00124

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:39 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Pathogenic:14

-

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ALPL: PM3:Very Strong, PM5, PM2:Supporting, PP3, PS3:Supporting -

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 191 of the ALPL protein (p.Glu191Lys). This variant is present in population databases (rs121918007, gnomAD 1.7%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individuals with hypophosphatasia (PMID: 12357339, 15671102, 24569605). It has also been observed to segregate with disease in related individuals. This variant is also known as p.Glu174Lys. ClinVar contains an entry for this variant (Variation ID: 13670). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt ALPL protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects ALPL function (PMID: 1409720, 20739387, 24569605). For these reasons, this variant has been classified as Pathogenic. -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 11, 2022

GeneDx

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Published functional studies demonstrate that E191K has delayed membrane anchoring (Brun-Heath et al., 2007) and relatively high residual alkaline phosphatase activity (56% and 88% of wildtype), though no dominant negative effect was observed (Zurutuza et al., 1999; Fauvert et al., 2009; Hofmann et al., 2014); Observed in homozygous state in large population cohorts (gnomAD) and in a clinically unaffected adult relative of an individual referred for genetic testing at GeneDx, supporting that this mild variant leads to disease only when a more severe variant is present on the opposite allele (in trans); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 24569605, 20739387, 1409720, 19500388, 11855933, 10332035, 18328985, 17719863, 11438998, 12357339, 29659871, 10679946, 19232125, 27920814, 10737975, 29236161, 15671102, 32160374, 31589614, 33083013, 8606878, 33101980, 34213743, 33093890, 33549410) -

May 27, 2022

Clinical Genetics Laboratory, Skane University Hospital Lund

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 13, 2016

Eurofins Ntd Llc (ga)

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 06, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Oct 02, 2021

Revvity Omics, Revvity

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 31, 2024

Mayo Clinic Laboratories, Mayo Clinic

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PP3, PM3_very_strong, PS3, PS4 -

Childhood hypophosphatasia Pathogenic:6

Sep 02, 2022

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Dominant negative and loss of function are known mechanisms of disease in this gene. Later-onset/mild disease is associated with monoallelic dominant negative variants or biallelic loss of function variants that retain residual enzyme activity, while early-onset/severe disease is caused by more complete loss of function variants (PMIDs: 20301329, 19500388). (I) 0108 - This gene is associated with both recessive and dominant disease. Severe forms of hypophosphatasia (perinatal and infantile) are generally associated with autosomal recessive disease, while the milder forms of hypophosphatasia (childhood, adult and odontohypophosphatasia) have been associated with both autosomal dominant and recessive disease (PMID: 19500388, 23688511). (I) 0112 - The condition associated with this gene has incomplete penetrance (PMID: 20301329). (I) 0115 - Variants in this gene are known to have variable expressivity (PMID: 20301329). (I) 0200 - Variant is predicted to result in a missense amino acid change from glutamic acid to lysine. (I) 0251 - This variant is heterozygous. (I) 0305 - Variant is present in gnomAD v2 >=0.01 and <0.03 for a recessive condition (689 heterozygotes, 5 homozygotes). (I) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v2) (1 heterozygote, 0 homozygotes). (I) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0600 - Variant is located in the annotated alkaline phosphatase domain (DECIPHER). (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This is a well-established pathogenic variant and has been observed in many individuals with hypophophatasia (ClinVar, PMIDs: 32973344, 32811521) . (SP) 1002 - This variant has moderate functional evidence supporting abnormal protein function. Site directed mutagenesis studies have shown this variant has residual activity of 56% compared to wild type and is thought to be a moderate allele (PMID: 19500388). (SP) 1101 - Very strong and specific phenotype match for this individual. (SP) 1206 - This variant has been shown to be paternally inherited (by segregation analysis, VCGS #22G000749). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign -

Jun 13, 2022

MGZ Medical Genetics Center

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 01, 2002

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Feb 18, 2021

Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.571G>A (p.Glu191Lys) variant in the ALPL gene is observed at a minor allele frequency (MAF) of 1.6% in the European (Finnish) population, including 3 homozygous individuals (https://gnomad.broadinstitute.org/variant/1-21890632-G-A). This variant has been reported in multiple individuals affected with autosomal recessive hypophosphatasia and observed to segregate with the disease in family studies (PMID: 12357339, PMID: 24569605). In vitro functional studies have suggested this variant mildly reduced the alkaline phosphatase (ALP) activity (PMID: 24569605). -

Oct 27, 2015

Division of Human Genetics, Children's Hospital of Philadelphia

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: research

- -

Jan 01, 2019

Institute of Human Genetics, University of Leipzig Medical Center

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypophosphatasia Pathogenic:5 Other:1

Dec 10, 2018

Illumina Laboratory Services, Illumina

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The ALPL c.571G>A (p.Glu191Lys) missense variant, also known as p.Glu174Lys, is a well-documented pathogenic variant. It was first identified by Henthorn et al. (1992) in seven out of 46 patients with variable clinical presentation. At least four of these patients were compound heterozygotes for the p.Glu191Lys variant and a second variant, while zygosity was not confirmed in other patients. These patients represented three clinical forms of hypophosphatasia: perinatal (lethal), childhood, and adult and showed autosomal recessive inheritance. Hérasse et al. (2002) reported that the p.Glu191Lys variant is a recurrent variant found in approximately 7% of affected Caucasian chromosomes. In this patient population, the p.Glu191Lys variant was seen in 31% of patients with mild hypophosphatasia (child, adult, and odonto forms). The p.Glu191Lys variant is found at a frequency of 0.01995 in the European (Finnish) population of the Exome Aggregation Consortium. In vitro functional studies performed by Fauvert et al. (2009) showed that the p.Glu191Lys variant has a residual activity of 56% compared to wild type. Based on the collective evidence, the p.Glu191Lys variant is classified as pathogenic for hypophosphatasia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. -

Jan 06, 2020

Reproductive Health Research and Development, BGI Genomics

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: curation

NM_000478.4:c.571G>A in the ALPL gene has an allele frequency of 0.017 in European(Finnish) subpopulation in the gnomAD database. Functional studies demonstrate that c.571G>A has reduced alkaline phosphatase activity due to structural disturbances and delay in membrane anchoring (PMID:17719863). It was detected in multiple individuals with autosomal recessive hypophosphatasia, compound heterozygous with p.Gly334Asp (PMID: 24569605), c.186G>C (p.M45I) (PMID: 15671102). The patient's phenotype is highly specific for ALPL gene (PMID: 15671102). Co-segregation evidence in a pedigree,one patient was affected and two sister unaffected (PMID:15671102). Pathogenic computational verdict because pathogenic predictions from DANN, DEOGEN2, EIGEN, FATHMM-MKL, MVP, MutationTaster, PrimateAI and REVEL. Phenotype date Taken together, we interprete this variant as Pathogenic/Likely pathogenic variant. ACMG/AMP criteria applied: PS3; PM3_Strong; PP1; PP4; PP3. -

Feb 17, 2016

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Feb 15, 2024

Baylor Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Adult hypophosphatasia Pathogenic:4

Nov 04, 2021

Undiagnosed Diseases Network, NIH

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Oct 01, 2002

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

May 04, 2022

Mendelics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 27, 2024

Baylor Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Infantile hypophosphatasia Pathogenic:3

Oct 01, 2002

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Nov 12, 2019

Myriad Genetics, Inc.

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NM_000478.4(ALPL):c.571G>A(E191K, aka E174K) is classified as pathogenic in the context of hypophosphatasia. Sources cited for classification include the following: PMID 25731960, 11438998, 19232125, 10679946, 11855933 and 10332035. Classification of NM_000478.4(ALPL):c.571G>A(E191K, aka E174K) is based on the following criteria: This is a well-established pathogenic variant in the literature that has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. -

Feb 01, 2024

Department of Pediatrics, Taizhou Central Hospital, Taizhou University Hospital

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Childhood hypophosphatasia;C0268412:Infantile hypophosphatasia;C0268413:Adult hypophosphatasia Pathogenic:2

Apr 08, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

- -

Oct 31, 2018

Fulgent Genetics, Fulgent Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

ALPL-related disorder Pathogenic:1

Aug 23, 2024

PreventionGenetics, part of Exact Sciences

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

The ALPL c.571G>A variant is predicted to result in the amino acid substitution p.Glu191Lys. This variant, alternatively referred to as p.Glu174Lys using legacy nomenclature, has been reported in the compound heterozygous state in numerous individuals with hypophosphatasia (HPP), predominantly childhood, adult and odontohypophosphatasia forms (see, for example, Henthorn et al. 1992. PubMed ID: 1409720, reported as 747A (p.Glu174Lys); Fauvert et al. 2009. PubMed ID: 19500388; Hofmann et al. 2014. PubMed ID: 24569605). It has also been reported in the heterozygous state in individuals with odontohypophosphatasia (Fauvert et al. 2009. PubMed ID: 19500388). This variant was also shown to segregate with HPP in two families (Henthorn et al. 1992. PubMed ID: 1409720; Hofmann et al. 2014. PubMed ID: 24569605). Functional studies using COS7 and HEK293 cells show mild reduction in tissue non-specific alkaline phosphatase (TNSALP) activity and also indicate this variant does not result in a dominant-negative effect. It is speculated that phenotypic variability is related to either an unidentified second variant or varying alkaline phosphatase tolerance thresholds (Fauvert et al. 2009. PubMed ID: 19500388; Hofmann et al. 2014. PubMed ID: 24569605). An alternate nucleotide change affecting the same amino acid, p.Glu191Gly (p.Glu174Gly using legacy nomenclature), has been reported in a patient with HPP (Goseki-Sone et al. 1998. PubMed ID: 9452105, reported as p.Glu174Gly; Michigami et al. 2019. PubMed ID: 31707452). This variant is reported in 1.7% of alleles in individuals of European (Finnish) descent in gnomAD, including 5 homozygotes. Reduced penetrance and expressivity is known in ALPL-related disease. This variant is interpreted as pathogenic. -

Osteogenesis imperfecta Pathogenic:1

Aug 13, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases Pathogenic:1

Aug 02, 2022

Ambry Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.571G>A (p.E191K) alteration is located in exon 6 (coding exon 5) of the ALPL gene. This alteration results from a G to A substitution at nucleotide position 571, causing the glutamic acid (E) at amino acid position 191 to be replaced by a lysine (K). Based on data from gnomAD, the A allele has an overall frequency of 0.25% (699/282574) total alleles studied. The highest observed frequency was 1.65% (414/25032) of European (Finnish) alleles. This variant, also described as E174K in literature, is a common founder mutation accounting for up to approximately 10% of disease-causing mutations in the ALPL gene (H&eacute;rasse, 2002; Mornet, 2021). This variant has been reported in the heterozygous (Hofmann, 2014; Taillandier, 2018; Mornet, 2021; Ambry internal data) and compound heterozygous (Henthorn, 1992; Schalin-J&auml;ntti, 2010; Hofmann, 2014; Zurutuza, 1999; Mornet, 2021; Sperelakis-Beedham, 2021) states in individuals with hypophosphatasia and low alkaline phosphatase, with the clinical severity correlating with degree of loss of function. This amino acid position is not well conserved in available vertebrate species. Multiple in vitro functional studies using transient expression in cells show slightly reduced activity consistent with a mild loss of function allele based on comparison to wild type and pathogenic controls (Hofmann, 2014; Zurutuza, 1999; Del Angel, 2020). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic. -

See cases Pathogenic:1

Dec 16, 2021

Institute of Human Genetics, University Hospital Muenster

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ACMG categories: PS3,PM1,PP3,PP5,BS1 -

Odontohypophosphatasia Pathogenic:1

-

Centogene AG - the Rare Disease Company

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Pathogenic	0.44
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.81	D;.;.;D
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	.;D;D;D
MetaRNN	Benign	0.015	T;T;T;T
MetaSVM	Pathogenic	0.89	D
MutationAssessor	Benign	1.5	L;.;.;L
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-2.2	N;N;N;N
REVEL	Pathogenic	0.84
Sift	Benign	0.058	T;T;T;T
Sift4G	Benign	0.21	T;T;T;T
Polyphen		0.97	D;.;.;D
Vest4		0.91
MVP		0.95
MPC		1.1
ClinPred		0.084	T
GERP RS		5.2
Varity_R		0.30
gMVP		0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs121918007; hg19: chr1-21890632;