rs11575937

chr1-156136985-G-Achr1-156136985-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1 PM2 PM5 PP2 PP5

The NM_170707.4(LMNA):c.1445G>A(p.Arg482Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,614,080 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R482W) has been classified as Pathogenic.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LMNA NM_170707.4 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:17 U:1 O:1
• Conservation: PhyloP100: 4.19

Genes affected

LMNA (HGNC:6636): (lamin A/C) The protein encoded by this gene is part of the nuclear lamina, a two-dimensional matrix of proteins located next to the inner nuclear membrane. The lamin family of proteins make up the matrix and are highly conserved in evolution. During mitosis, the lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. Lamin proteins are thought to be involved in nuclear stability, chromatin structure and gene expression. Vertebrate lamins consist of two types, A and B. Alternative splicing results in multiple transcript variants. Mutations in this gene lead to several diseases: Emery-Dreifuss muscular dystrophy, familial partial lipodystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy, Charcot-Marie-Tooth disease, and Hutchinson-Gilford progeria syndrome. [provided by RefSeq, May 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PM1: In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 11 uncertain in NM_170707.4
• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr1-156136984-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 14489.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• PP2: Missense variant where missense usually causes diseases, LMNA
• PP5: Variant 1-156136985-G-A is Pathogenic according to our data. Variant chr1-156136985-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 14486.We mark this variant Likely_pathogenic, oryginal submissions are: {Pathogenic=13, not_provided=1, Uncertain_significance=1}. Variant chr1-156136985-G-A is described in Lovd as [Pathogenic]. Variant chr1-156136985-G-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMNA	NM_170707.4	c.1445G>A	p.Arg482Gln	missense_variant	8/12	ENST00000368300.9
LMNA	NM_005572.4	c.1445G>A	p.Arg482Gln	missense_variant	8/10	ENST00000677389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMNA	ENST00000368300.9	c.1445G>A	p.Arg482Gln	missense_variant	8/12	1	NM_170707.4	P1
LMNA	ENST00000677389.1	c.1445G>A	p.Arg482Gln	missense_variant	8/10		NM_005572.4

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461876 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152204 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74358

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000167 Hom.: 0

Bravo AF: 0.0000302

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:17 Uncertain:1 Other:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Familial partial lipodystrophy, Dunnigan type Pathogenic:5

Pathogenic, no assertion criteria provided	literature only	OMIM	Mar 01, 2013	- -
Pathogenic, no assertion criteria provided	research	CSER _CC_NCGL, University of Washington	Jun 01, 2014	- -
Pathogenic, criteria provided, single submitter	clinical testing	Institute of Human Genetics, University of Leipzig Medical Center	Feb 19, 2024	Criteria applied: PS4,PM5_STR,PS3_MOD,PM2_SUP,PP3,PP4 -
Pathogenic, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	Nov 12, 2020	DNA sequence analysis of the LMNA gene demonstrated a sequence change, c.1445G>A, in exon 8 that results in an amino acid change, p.Arg482Gln. This sequence change has been described in the EXAC database with a low population frequency of 0.001% (dbSNP rs11575937). The p.Arg482Gln variant in LMNA has been reported in multiple families with Dunnigan-type familial partial lipodystrophy (FPLD) and co-segregated with affected individuals (PMIDs: 10587585, 10999791, 19418082, 19859838, 20130076, 20625965, 26662654). Transgenic mice expressing the p.Arg482Gln variant showed increase blood insulin levels, reduced insulin sensitivity, and impaired adipocyte differentiation, consistent with the clinical phenotypes observed in patients (PMID: 19201734). Furthermore, other missense changes at this same position (p.Arg482Trp and p.Arg482Leu) have also been implicated in familial partial lipodystrophy (PMIDs: 10655060, 10739751). -
Pathogenic, criteria provided, single submitter	clinical testing	Neuberg Centre For Genomic Medicine, NCGM	-	The missense variant p.R482Q in LMNA (NM_170707.4) has been previously reported in individuals with familial partial lipodystrophy type 2 and is a mutational hot spot for the same(Jacob KN et al).Mice models are consistent with a phenotype of FPL D (Wojtanik 2009).It has been submitted to ClinVar as Pathogenic .The missense variant c.1445G>A (p.R482Q) in LMNA (NM_170707.4) is not observed in the large population cohorts of the gnomAD and 1000 Genomes datasets (Exome Aggregation Consortium et al., 2016; 1000 Genomes Consortium et al., 2015)The p.R482Q variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.R482Q missense variant is predicted to be damaging by both SIFT and PolyPhen2. The arginine residue at codon 482 of LMNA is conserved in all mammalian species. The nucleotide c.1445 in LMNA is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic. -

not provided Pathogenic:4 Other:1

not provided, no classification provided	literature only	Epithelial Biology; Institute of Medical Biology, Singapore	-	- -
Pathogenic, criteria provided, single submitter	clinical testing	GeneDx	May 06, 2022	Observed in apparent homozygous state in one individual with generalized lipodystrophy and Emery-Dreifuss muscular dystrophy in published literature (Wiltshire et al., 2013); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Transgenic mice harboring this variant develop a syndrome that resembles many of the features of human familial partial lipodystrophy (Wojtanik et al., 2009); Reported as pathogenic by several other clinical laboratories in ClinVar (ClinVar Variant ID# 14486; ClinVar); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30275911, 16181372, 10999845, 22700598, 26662654, 28641778, 17893350, 29578370, 19859838, 25637381, 23427149, 10999791, 20130076, 11792809, 19201734, 23313286, 20625965, 24375749, 19418082, 10587585, 12647844, 28679633, 25741868, 18728124, 10739751, 19011997, 12524233, 28663758, 30165155, 31194872, 28199729, 27485410, 28450900, 11136544, 11078466, 10655060, 10810087, 31836692, 31447099, 33502018, 32041611, 16415042, 10939567) -
Pathogenic, criteria provided, single submitter	clinical testing	AiLife Diagnostics, AiLife Diagnostics	Dec 30, 2021	- -
Pathogenic, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Aug 11, 2017	The LMNA c.1445G>A, p.Arg482Gln variant (rs11575937) has been reported in multiple families with familial partial lipodystrophy (Dunnigan-type) (Cao 2000, Drac 2010, Gamberini 2008, Hegele 2000, Hegele 2000b, Imachi 2009, Ludtke 2005, Shackleton 2000, Speckman 2000, Vigouroux 2000), and co-segregated with affected individuals (Cao 2000, Hegele 2000, Speckman 2000). Other missense variants at this position (p.Arg482Trp and p.Arg482Leu) have also been implicated in familial partial lipodystrophy (Hegele 2000b, Shackleton 2000, Speckman 2000, Vigouroux 2000). The variant protein appears to have no significant impact on the structural integrity of the nucleus, but appears to decrease Lamin B2 expression (Zwerger 2013). Transgenic mice expressing the human variant protein shows increase blood insulin levels, reduced insulin sensitivity, and impaired adipocyte differentiation, consistent with the clinical phenotypes in patients (Wojtanik 2009). The p.Arg482Gln variant is listed as pathogenic in ClinVar (Variation ID: 14486), and observed once in the Exome Variant Server (1/13006 alleles) and Genome Aggregation Database (1/246132 alleles). Based on the above information, the variant is classified as pathogenic. References: Cao H et al. Nuclear lamin A/C R482Q mutation in canadian kindreds with Dunnigan-type familial partial lipodystrophy. Hum Mol Genet. 2000; 9(1):109-12. Gambineri A et al. Monogenic polycystic ovary syndrome due to a mutation in the lamin A/C gene is sensitive to thiazolidinediones but not to metformin. Eur J Endocrinol. 2008; 159(3):347-53. Hegele R et al. Association between nuclear lamin A/C R482Q mutation and partial lipodystrophy with hyperinsulinemia, dyslipidemia, hypertension, and diabetes. Genome Res. 2000; 10(5):652-8. Hegele R et al. Heterogeneity of nuclear lamin A mutations in Dunnigan-type familial partial lipodystrophy. J Clin Endocrinol Metab. 2000b; 85(9):3431-5. Imachi H et al. A case of Dunnigan-type familial partial lipodystrophy (FPLD) due to lamin A/C (LMNA) mutations complicated by end-stage renal disease. Endocrine. 2009; 35(1):18-21. Ludtke A et al. Hepatic steatosis in Dunnigan-type familial partial lipodystrophy. Am J Gastroenterol. 2005; 100(10):2218-24. Shackleton S et al. LMNA, encoding lamin A/C, is mutated in partial lipodystrophy. Nat Genet. 2000; 24(2):153-6. Speckman R et al. Mutational and haplotype analyses of families with familial partial lipodystrophy (Dunnigan variety) reveal recurrent missense mutations in the globular C-terminal domain of lamin A/C. Am J Hum Genet. 2000; 66(4):1192-8. Vigouroux C et al. Lamin A/C gene: sex-determined expression of mutations in Dunnigan-type familial partial lipodystrophy and absence of coding mutations in congenital and acquired generalized lipoatrophy. Diabetes. 2000; 49(11):1958-62. Wojtanik K et al. The role of LMNA in adipose: a novel mouse model of lipodystrophy based on the Dunnigan-type familial partial lipodystrophy mutation. J Lipid Res. 2009; 50(6):1068-79. Zwerger M et al. Myopathic lamin mutations impair nuclear stability in cells and tissue and disrupt nucleo-cytoskeletal coupling. Hum Mol Genet. 2013; 22(12):2335-49. -
Pathogenic, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jan 04, 2017	- -

Emery-Dreifuss muscular dystrophy 3, autosomal recessive Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 01, 2013

- -

Laminopathy Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Apr 05, 2019

The p.Arg482Gln variant in LMNA has been reported in at least 20 individuals with Dunnigan-type familial partial lipodystrophy (FPLD) and segregated with disease in more than 40 affected family members from at least 8 families (Cao 2000, Hegel 2000, Speckman 2000, Vigouroux 2000, Ludtke 2005, Gambineri 2008, Mory 2012, Wiltshire 2013, Lewandowski 2015). Other clinical laboratories have reported this variant in ClinVar (Variation ID 14486). This variant has also been identified in 1/111632 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs11575937). Please note that for diseases with clinical variability, reduced penetrance, or recessive inheritance, pathogenic variants may be present at a low frequency in the general population. Transgenic mice with the p.Arg482Gln variant of LMNA have a phenotype consistent FPLD (Wojtanik 2009). In summary, this variant meets criteria to be classified as pathogenic for FPLD in an autosomal dominant manner based on presence in multiple affected individuals, segregation studies, low frequency in the general population and in vivo functional studies. The ACMG/AMP Criteria applied: PS4, PP1_strong, PM2, PS3_moderate (Richards 2015). -

Hutchinson-Gilford syndrome;C0406585:Lethal tight skin contracture syndrome;C0410190:Emery-Dreifuss muscular dystrophy 2, autosomal dominant;C0796031:Dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome;C1449563:Dilated cardiomyopathy 1A;C1720860:Familial partial lipodystrophy, Dunnigan type;C1854154:Charcot-Marie-Tooth disease type 2B1;C1857829:Heart-hand syndrome, Slovenian type;C2750035:Emery-Dreifuss muscular dystrophy 3, autosomal recessive;C2750785:Congenital muscular dystrophy due to LMNA mutation;C5399785:Mandibuloacral dysplasia with type A lipodystrophy Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 31, 2018

- -

Charcot-Marie-Tooth disease type 2 Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Invitae

Jan 05, 2024

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 482 of the LMNA protein (p.Arg482Gln). This variant is present in population databases (rs11575937, gnomAD 0.0009%). This missense change has been observed in individuals with autosomal recessive Emery-Dreifuss muscular dystrophy (EDMD) and autosomal dominant familial lipodystrophy type 2 (FLPD2) (PMID: 10587585, 10999791, 19418082, 19859838, 20130076, 20625965, 23313286, 26662654). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 14486). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LMNA protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects LMNA function (PMID: 19201734, 20130076). For these reasons, this variant has been classified as Pathogenic. -

Monogenic diabetes Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Translational Genomics Laboratory, University of Maryland School of Medicine

Dec 07, 2017

The c.1445G>A variant in codon 482 (exon 8 of the RefSeq gene) of the Lamin A/C gene, LMNA, results in the substitution of Arginine to Glutamine. Mutations in the LMNA gene have been found to cause multiple disorders, collectively known as A-type laminopathies, that have overlapping signs and symptoms (23853504, 20074070, OMIM, 16364671). A-type laminopathies include familial partial lipodystrophy type 2 (FPLD2, also called familial partial lipodystrophy, Dunnigan type), Limb-Girdle muscular dystrophy type 1B, Emery-Dreifuss muscular dystrophy (EDMD), Charcot-Marie-Tooth type 2B1 disease, Hutchinson-Gilford progeria, Heart-hand syndrome, Slovenian type, mandibuloacral dysplasia, Malouf syndrome, and familial dilated cardiomyopathy (23853504, 20074070, OMIM). To date, no clear genotype-phenotype correlations have been identified (23853504, 20074070). The c.1445G>A variant has been identified in multiple individuals over multiple generations in families with clinical diagnoses of FPLD2 (22700598, 10868844, 10999845, 10587585, 10739751, 10655060). This variant was also found in the homozygous state in an individual with FPLD2 and autosomal recessive-EDMD (23313286). A different amino acid change at codon 482, Arg482Trp, has also been shown to segregate with FPLD2 (23853504, 22700598, 10999845, 10739751, 10655060). Approximately 75% of patients with FPLD2 have a mutation at Arg482, making it a mutational hotspot for FPLD2 (16364671). Multiple lines of computational evidence (SIFT, LRT, MutationTaster, FATHMM, MetaSVM, MetalR, GERP, CADD) predict the c.1445G>A variant is probably damaging to the protein structure, function, or protein-protein interaction. Indeed, functional studies of the Arg482Gln mutant protein, as well as the Arg482Trp protein, demonstrated a failure of adipocyte cell differentiation (16415042). A transgenic mouse harboring the Arg482Gln mutation recapitulates the FPLD2 phenotype and studies confirmed a lack of adipocyte renewal (19201734). ACMG criteria = PS3, PS4, PP1-strong, PM1, PM5, PP3 -

LMNA-related disorder Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 22, 2023

The LMNA c.1445G>A variant is predicted to result in the amino acid substitution p.Arg482Gln. This variant has been reported in the homozygous state in two Hutterite siblings that presented with an atypical Emery-Dreifuss muscular dystrophy and in the heterozygous state in other family members with familial partial lipodystrophy and abnormal lipid profiles (Wiltshire et al. 2013. PMID: 23313286). Of note, the authors tested for the c.1445G>A variant in 482 Dariusleut and Leherleut Hutterites in Alberta and found the overall carrier frequency to be 1.45%. In addition, this variant in the heterozygous state has been reported in several unrelated families of other ethnicities to be causative for familial partial lipodystrophy in an autosomal dominant manner (Cao and Hegele. 2000. PubMed ID: 10587585; Hegele et al. 2000. PubMed ID: 10999791; Speckman et al. 2000. PubMed ID: 10739751; http://www.LOVD.nl/LMNA). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. In summary, the c.1445G>A variant is pathogenic for a spectrum of laminopathies in both the heterozygous and homozygous state. -

Dilated cardiomyopathy 1A Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Institute of Human Genetics, University of Leipzig Medical Center

Jan 12, 2022

_x000D_ Criteria applied: PS3, PS4, PM5_STR, PM1, PM2_SUP, PP3 -

Cardiovascular phenotype Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2020

The p.R482Q pathogenic mutation (also known as c.1445G>A), located in coding exon 8 of the LMNA gene, results from a G to A substitution at nucleotide position 1445. The arginine at codon 482 is replaced by glutamine, an amino acid with highly similar properties. This mutation has been detected in many unrelated individuals with familial partial lipodystrophy (FPLD) and segregated with FPLD several families (Cao H et al. Hum Mol Genet, 2000 Jan;9:109-12; Shackleton S et al. Nat Genet, 2000 Feb;24:153-6; Gambineri A et al. Eur J Endocrinol, 2008 Sep;159:347-53; Boschmann M et al. J Clin Endocrinol Metab, 2010 Apr;95:1634-43; Lewandowski KC et al. Endokrynol Pol, 2015;66:550-4; Akinci B et al. Metabolism, 2017 07;72:109-119; Kwapich M et al. Diabetes Metab, 2019 09;45:382-389; Sekizkardes H et al. J Clin Endocrinol Metab, 2019 08;104:3068-3076). This mutation has also been detected in the homozygous state in siblings reported to have atypical autosomal recessive Emery-Dreifuss muscular dystrophy (Wiltshire KM et al. Neuromuscul Disord, 2013 Mar;23:265-8). In addition, a transgenic mouse model expressing this mutation recapitulated FPLD phenotype (Wojtanik KM et al. J Lipid Res, 2009 Jun;50:1068-79). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. -

Cardiomyopathy Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Color Diagnostics, LLC DBA Color Health

Oct 05, 2023

This missense variant replaces arginine with glutamine at codon 482 of the lamin A/C proteins. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). This variant has been shown to cause partial lipodystrophy phenotype in a transgenic mouse model (PMID: 19201734). This variant has been reported in many individuals affected with familial partial lipodystrophy (PMID: 10587585, 10999791, 19418082, 19859838, 20130076, 20625965, 26662654, 30165155, 31194872, 33803652, 34340952, 34865644, 35291351, 37679847) and in individuals affected with Emery-Dreifuss muscular dystrophy (PMID: 23313286). However, this variant has not been reported in individuals affected with cardiomyopathy in the literature. This variant has been identified in 1/246132 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as a Variant of Uncertain Significance for autosomal dominant cardiomyopathy, although it is known to cause familial partial lipodystrophy (ClinVar variation ID: 14486). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
CardioboostCm	Benign	0.0086
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.37
Cadd	Pathogenic	31
Dann	Pathogenic	1.0
Eigen	Benign	0.060
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D;D;D;D
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.50	T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.71	D
MutationAssessor	Benign	1.3	L;L;L;L;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.99	N;N;N;N;N;N;N;N
REVEL	Uncertain	0.56
Sift	Benign	0.037	D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.035	D;D;D;D;T;T;T;D
Polyphen		0.097	B;B;B;.;.;B;.;.
Vest4		0.64
MVP		0.97
MPC		0.41
ClinPred		0.64	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.67
gMVP		0.77

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: rs11575937; hg19: chr1-156106776;