9-36217448-C-T

Variant names:

• chr9-36217448-C-T
• rs121908627
• NM_001128227.3:c.2179G>A

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 9P and 2B. PP2 PP5_Very_Strong BP4 BS1_Supporting

The NM_005476.7(GNE):​c.2086G>A​(p.Val696Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000745 in 1,614,208 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).

• Frequency:
  • Genomes: 𝑓 0.00046 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00078 (11 hom.)
• Consequence: GNE NM_005476.7 missense
• Clinical Significance: Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:26 U:1 O:1
• Conservation: PhyloP100: 7.52

Genes affected

GNE (HGNC:23657): (glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase) The protein encoded by this gene is a bifunctional enzyme that initiates and regulates the biosynthesis of N-acetylneuraminic acid (NeuAc), a precursor of sialic acids. It is a rate-limiting enzyme in the sialic acid biosynthetic pathway. Sialic acid modification of cell surface molecules is crucial for their function in many biologic processes, including cell adhesion and signal transduction. Differential sialylation of cell surface molecules is also implicated in the tumorigenicity and metastatic behavior of malignant cells. Mutations in this gene are associated with sialuria, autosomal recessive inclusion body myopathy, and Nonaka myopathy. Alternative splicing of this gene results in transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

CLTA (HGNC:2090): (clathrin light chain A) Clathrin is a large, soluble protein composed of heavy and light chains. It functions as the main structural component of the lattice-type cytoplasmic face of coated pits and vesicles which entrap specific macromolecules during receptor-mediated endocytosis. This gene encodes one of two clathrin light chain proteins which are believed to function as regulatory elements. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 8 and 12. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PP2: Missense variant in the GNE gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 44 curated pathogenic missense variants (we use a threshold of 10). The gene has 1 curated benign missense variants. Gene score misZ: 2.5904 (below the threshold of 3.09). Trascript score misZ: 3.9915 (above the threshold of 3.09). GenCC associations: The gene is linked to macrothrombocytopenia, isolated, platelet-type bleeding disorder 19, sialuria, GNE myopathy.
• PP5: Variant 9-36217448-C-T is Pathogenic according to our data. Variant chr9-36217448-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 6028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-36217448-C-T is described in Lovd as [Likely_pathogenic]. Variant chr9-36217448-C-T is described in Lovd as [Pathogenic]. Variant chr9-36217448-C-T is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.010822177). . Strength limited to SUPPORTING due to the PP5.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00046 (70/152326) while in subpopulation SAS AF= 0.0139 (67/4820). AF 95% confidence interval is 0.0112. There are 1 homozygotes in gnomad4. There are 50 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNE	NM_001128227.3	c.2179G>A	p.Val727Met	missense_variant	Exon 12 of 12	ENST00000396594.8	NP_001121699.1
GNE	NM_005476.7	c.2086G>A	p.Val696Met	missense_variant	Exon 12 of 12	ENST00000642385.2	NP_005467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNE	ENST00000396594.8	c.2179G>A	p.Val727Met	missense_variant	Exon 12 of 12	1	NM_001128227.3	ENSP00000379839.3
GNE	ENST00000642385.2	c.2086G>A	p.Val696Met	missense_variant	Exon 12 of 12		NM_005476.7	ENSP00000494141.2

Frequencies

GnomAD3 genomes AF: 0.000453 AC: 69 AN: 152208 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00167 AC: 419 AN: 251452 Hom.: 2 AF XY: 0.00226 AC XY: 307 AN XY: 135898

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: 0.0134

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000775 AC: 1133 AN: 1461882 Hom.: 11 Cov.: 31 AF XY: 0.00113 AC XY: 822 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0123

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.000844

GnomAD4 genome AF: 0.000460 AC: 70 AN: 152326 Hom.: 1 Cov.: 32 AF XY: 0.000671 AC XY: 50 AN XY: 74490

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0139

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000793

ExAC AF: 0.00194 AC: 235

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:26 Uncertain:1 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

GNE myopathy Pathogenic:13 Uncertain:1 Other:1

Dec 04, 2018

Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

The observed variant c.2179G>A (p.V727M) is a known pathogenic variant found very commonly in Indian patients related to GNE Myopathy, has been observed in compound heterozygous status with the other observed variant c.97G>T (p.E33X), which has not been reported in 1000 Genomes and ExAC databases but its in-silico prediction was found to be pathogenic by PolyPhen-2, MutationTaster2 and SIFT. -

Jun 13, 2019

Counsyl

Significance: Uncertain significance

Review Status: flagged submission

Collection Method: clinical testing

- -

Jun 22, 2023

Neuberg Centre For Genomic Medicine, NCGM

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The missense c.2086G>Ap.Val696Met variant in GNE gene has been reported previously in compound heterozygous state in multiple individuals affected with GNE myopathy Garland J, et al., 2017; Khadilkar SV, et al., 2017; Zhu W, et al., 2017. This variant has been observed to segregate with disease in related individuals Boyden SE, et al., 2011. The variant has been reported as a founder mutation in South-East Asian populations, and it is one of the most frequent alleles in Indian patients Bhattacharya S, et al., 2018. The p.Val696Met variant has been reported with allele frequency of 0.2% in gnomAD Exomes. This variant has been reported to the ClinVar database as Likely Benign / Uncertain Significance / Likely Pathogenic / Pathogenic multiple submissions. The amino acid Val at position 696 is changed to a Met changing protein sequence and it might alter its composition and physico-chemical properties. Multiple lines of computational evidences Polyphen - Probabaly damaging, SIFT - Damaging and MutationTaster - Disease causing predict a damaging effect on protein structure and function for this variant. The reference amino acid change at this position on the GNE gene is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic. -

Sep 01, 2001

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

-

Lifecell International Pvt. Ltd

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

A Heterozygous Missense variant c.2086G>A in Exon 12 of the GNE gene that results in the amino acid substitution p.Val696Met was identified. The observed variant has a maximum allele frequency of 0.00167/0.00010% in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is medium, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Pathogenic (variant ID: 430940). This variant was reported among patients for myopathies in the Indian Subcontinent (Chakravorty S et al., 2020). Based on the above evidence this variant has been classified as Pathogenic according to the ACMG guidelines. -

Mar 30, 2024

Baylor Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 20, 2024

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

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: GNE c.2179G>A (p.Val727Met) results in a conservative amino acid change located in the N-acetylmannosamine kinase domain (UniProt) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0017 in 251452 control chromosomes, predominantly at a frequency of 0.013 within the South Asian subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 10-fold of the estimated maximal expected allele frequency for a pathogenic variant in GNE causing Inclusion Body Myopathy 2 phenotype (0.0011), suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. However, the variant, c.2179G>A, has also been reported in the literature in numerous compound heterozygous individuals affected with Inclusion Body Myopathy 2 (IBM2) (e.g. Eisenberg_2003, Voermans_2010, Boyden_2011, Cerino_2015, Zhu_2017, Garland_2017, Bhattacharya_2018, Chakravorty_2020), and in some of these reports the variant was noted to segregate with the diseases in the affected families (Boyden_2011, Zhu_2017, Garland_2017). The variant has been reported as a founder mutation in South-East Asian populations, and it is one of the most frequent alleles in Indian patients (see e.g. Bhattacharya_2018, Chakravorty_2020). The variant was also reported in a few homozygous patients (Cerino_2015, Bhattacharya_2018, Chakravorty_2020). However, in at least one of these cases the variant was present on both chromosomes in combination with another variant, thus making this case compound heterozygous; authors of this study concluded that the near absence of homozygous p.Val727Met patients probably suggests that disease may not develop in such individuals (Bhattacharya_2018). A recent genotype-phenotype correlation study concluded that patients carrying the variant, p.Val727Met, appear to have a milder phenotype with later onset (Pogoryelova_2018). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 29480215, 21708040, 27858732, 33250842, 12497639, 28717665, 27535533, 30842975, 20175955, 27829678, Attri_2021). ClinVar contains an entry for this variant (Variation ID: 6028). Based on the evidence outlined above, this variant likely represents a hypomorphic allele, which in compound heterozygous state, together with another more severe variant in trans, can cause IBM2 and related phenotypes, however in homozygous form it might not (always) result in disease; therefore, the variant was classified as likely pathogenic. -

-

Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 06, 2020

Reproductive Health Research and Development, BGI Genomics

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: curation

NM_001128227.2:c.2179G>A in the GNE gene has an allele frequency of 0.013 in South Asian subpopulation in the gnomAD database. This variant has been reported in the compound heterozygous state with p.R160X in a patient with GNE myopathy (PMID: 25182749), and in another four cases in the compound heterozygous state with c. 910G>A, c. 1258C>T, c. 1539G>A, and c. 1703G>T(PMID: 24005727). This variant has been reported to segregate with GNE myopathy in affected families (PMID: 21708040; 28717665; 27829678). Taken together, we interprete this variant as Pathogenic/Likely pathogenic variant. ACMG/AMP Criteria applied: PM3_Strong; PP1_Moderate; PP4. -

Oct 09, 2024

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: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Nonaka myopathy (MIM#605820) and Sialuria (MIM#269921). (I) 0108 - This gene is associated with both recessive and dominant disease. Variants associated with Sialuria (MIM#2699210) are located at codons Arg263 and Arg266 (PMID: 23842869). (I) 0200 - Variant is predicted to result in a missense amino acid change from alanine to valine. (I) 0251 - This variant is heterozygous. (I) 0305 - Variant is present in gnomAD (v2) >=0.01 and <0.03 for a recessive condition (418 heterozygotes, 2 homozygotes). (I) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v2) (252 heterozygotes, 0 homozygotes). (I) 0502 - Missense variant with conflicting in silico predictions and very? high conservation. (I) 0600 - Variant is located in an annotated kinase domain (PMID: 11528398). (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been observed as compound heterozygous in many individuals with GNE-related myopathy, and has also been observed as homozygous in at least three individuals with late onset myopathy (ClinVar, PMIDs: 11528398, 33250842, 27858732, 28320138). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign -

Jun 23, 2014

Division of Human Genetics, Children's Hospital of Philadelphia

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

This variant (c. 2086G>A; p.V696M) has been previously reported as a pathogenic variant in individuals of Indian and Thai origin. It has been shown to segregate with disease in at least one family, including 3 affected and 4 unaffected individuals (Eisenberg et al 2001; Boyden et al 2011: Liewluck et al 2006; Eisenberg et al 2003). -

-

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Apr 28, 2020

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 06, 2021

Genetics and Molecular Pathology, SA Pathology

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant has been associated with GNE myopathy when in combination with a pathogenic variant on the other allele. No current reports of affected individuals het or hom for this variant. -

Mar 01, 2017

GenePathDx, GenePath diagnostics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

34 years old female, no family history, started having frequent falls at the age of 29 years of age followed by progressively increasing weakness of lower limbs. The weakness appears to be more in distal areas than proximal limb and lower limb is affected more than upper limbs. Next generation DNA sequencing of peripheral blood sample has revealed the presence of two pathogenic variants c.2086 G>A and c.1571C>T in the GNE gene consistent with the diagnosis of Nonaka myopathy or inclusion body myopathy 2/ distal myopathy with rimmed vacuoles. -

not provided Pathogenic:5

Oct 15, 2020

Mayo Clinic Laboratories, Mayo Clinic

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 13, 2018

Eurofins Ntd Llc (ga)

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 02, 2023

Revvity Omics, Revvity

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 06, 2024

GeneDx

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31561939, 25002140, 20059379, 24796702, 24695763, 24707269, 11528398, 27535533, 27829678, 20175955, 19917666, 28717665, 27457812, 24005727, 29997562, 12497639, 16810679, 25182749, 25617006, 14972325, 21708040, 29480215, 30564623, 31589614, 33250842, 37366078, 35933247, 36344503, 33197058, 34825065, 31069529, 35723113, 35398442) -

Sep 01, 2021

CeGaT Center for Human Genetics Tuebingen

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sialuria;C1853926:GNE myopathy Pathogenic:4

Oct 31, 2018

Fulgent Genetics, Fulgent Genetics

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Baylor Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 15, 2015

Division of Human Genetics, Children's Hospital of Philadelphia

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

- -

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 727 of the GNE protein (p.Val727Met). This variant is present in population databases (rs121908627, gnomAD 1.4%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individual(s) with autosomal recessive GNE myopathy/distal myopathy with rimmed vacuoles (PMID: 11528398, 12497639, 20175955, 21708040, 23437777, 24005727, 25182749, 27829678, 28320138, 28717665). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is also known as p.Val696Met. ClinVar contains an entry for this variant (Variation ID: 6028). 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) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GNE protein function. For these reasons, this variant has been classified as Pathogenic. -

GNE-related disorder Pathogenic:2

Jun 06, 2023

PreventionGenetics, part of Exact Sciences

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The GNE c.2179G>A variant is predicted to result in the amino acid substitution p.Val727Met. This variant is also known as c.2086G>A, p.Val696Met using an alternative transcript NM_005476.5. This variant has been reported in many individuals in the compound heterozygous state to be causative for recessive GNE myopathy (Eisenberg et al. 2001. PubMed ID: 11528398; Chaouch et al. 2014. PubMed ID: 24695763; Boyden et al. 2011. PubMed ID: 21708040; Voermans et al. 2010. PubMed ID: 20175955). The c.2179G>A variant has a minor allele frequency of 1.36% in South Asian populations which is consistent with this variant likely being a pathogenic founder mutation in individuals of Indian and Thai descent (Nalini et al. 2013. PubMed ID: 24005727; Tanboon et al. 2014. PubMed ID: 24707269; Voermans et al. 2010. PubMed ID: 20175955). Variants in GNE are also associated with autosomal dominant sialuria (Leroy et al. 2001. PubMed ID: 11326336). Some patients with GNE myopathy were reported to have mild, asymptomatic thrombocytopenia (Mori-Yoshimura et al. 2014. PubMed ID: 25303967). Two recent studies report patients with severe congenital thrombocytopenia with no clinical evidence of GNE myopathy who harbored homozygous variants in GNE (Revel-Vilk et al. 2018. PubMed ID: 30171045; Futterer et al. 2018. PubMed ID: 29941673). In addition to large platelets, patients showed bruising and bleeding tendencies though platelet aggregation appeared to be unaffected. In summary, the c.2179G>A variant is pathogenic for recessive GNE myopathy and may also be associated with other GNE-related conditions. -

Jan 01, 2024

Daryl Scott Lab, Baylor College of Medicine

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PS4, PM3, PP1 -

Sialuria Pathogenic:1

May 04, 2022

Mendelics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sialuria;C1853926:GNE myopathy;C5935593:Thrombocytopenia 12 with or without myopathy Pathogenic:1

Apr 10, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Pathogenic	0.56
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.80	D;.;D;.;.;.;D
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	.;D;D;D;D;D;.
MetaRNN	Benign	0.011	T;T;T;T;T;T;T
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	2.9	M;.;M;.;.;.;M
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.52	.;N;N;.;N;N;N
REVEL	Pathogenic	0.86
Sift	Uncertain	0.0010	.;D;D;.;D;D;D
Sift4G	Uncertain	0.013	.;D;D;D;D;D;D
Polyphen		0.97	D;D;D;.;.;.;D
Vest4		0.68, 0.82, 0.73, 0.68, 0.72, 0.77
MutPred		0.84		Gain of sheet (P = 0.0827);.;Gain of sheet (P = 0.0827);.;.;.;Gain of sheet (P = 0.0827);
MVP		0.97
MPC		1.3
ClinPred		0.14	T
GERP RS		5.7
Varity_R		0.81
gMVP		0.90

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: rs121908627; hg19: chr9-36217445;