9-131523065-C-T

Position:

chr9-131523065-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000402686.8(POMT1):c.2137C>T(p.Arg713Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0128 in 1,611,524 control chromosomes in the GnomAD database, including 192 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R713H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0096 ( 14 hom., cov: 33)

Exomes 𝑓: 0.013 ( 178 hom. )

Consequence

POMT1
ENST00000402686.8 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 3.72

Variant links:

Genes affected

POMT1 (HGNC:9202): (protein O-mannosyltransferase 1) The protein encoded by this gene is an O-mannosyltransferase that requires interaction with the product of the POMT2 gene for enzymatic function. The encoded protein is found in the membrane of the endoplasmic reticulum. Defects in this gene are a cause of Walker-Warburg syndrome (WWS) and limb-girdle muscular dystrophy type 2K (LGMD2K). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2008]

POMT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016078085).

BP6

Variant 9-131523065-C-T is Benign according to our data. Variant chr9-131523065-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 95463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-131523065-C-T is described in Lovd as [Likely_benign]. Variant chr9-131523065-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00957 (1457/152306) while in subpopulation NFE AF= 0.0156 (1062/68012). AF 95% confidence interval is 0.0148. There are 14 homozygotes in gnomad4. There are 675 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMT1	NM_001077365.2 linkuse as main transcript	c.2137C>T	p.Arg713Cys	missense_variant	20/20	ENST00000402686.8	NP_001070833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POMT1	ENST00000402686.8 linkuse as main transcript	c.2137C>T	p.Arg713Cys	missense_variant	20/20	1	NM_001077365.2	ENSP00000385797	P1	Q9Y6A1-2

Frequencies

GnomAD3 genomes

AF:

0.00959

AC:

1459

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00256

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00975

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.00838

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0156

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00868

AC:

2169

AN:

249818

Hom.:

AF XY:

0.00910

AC XY:

1229

AN XY:

135128

show subpopulations

Gnomad AFR exome

AF:

0.00231

Gnomad AMR exome

AF:

0.00734

Gnomad ASJ exome

AF:

0.00150

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00338

Gnomad FIN exome

AF:

0.00748

Gnomad NFE exome

AF:

0.0136

Gnomad OTH exome

AF:

0.0108

GnomAD4 exome

AF:

0.0131

AC:

19094

AN:

1459218

Hom.:

178

Cov.:

AF XY:

0.0129

AC XY:

9376

AN XY:

725866

show subpopulations

Gnomad4 AFR exome

AF:

0.00218

Gnomad4 AMR exome

AF:

0.00750

Gnomad4 ASJ exome

AF:

0.00153

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00381

Gnomad4 FIN exome

AF:

0.00790

Gnomad4 NFE exome

AF:

0.0155

Gnomad4 OTH exome

AF:

0.00998

GnomAD4 genome

AF:

0.00957

AC:

1457

AN:

152306

Hom.:

Cov.:

AF XY:

0.00907

AC XY:

675

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00255

Gnomad4 AMR

AF:

0.00974

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00838

Gnomad4 NFE

AF:

0.0156

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.0124

Hom.:

Bravo

AF:

0.00930

TwinsUK

AF:

0.0146

AC:

ALSPAC

AF:

0.0130

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.0136

AC:

117

ExAC

AF:

0.00852

AC:

1034

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0137

EpiControl

AF:

0.0135

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 12, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jun 11, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 09, 2012	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	POMT1: PM5, BS1, BS2 -

Autosomal recessive limb-girdle muscular dystrophy type 2K

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Walker-Warburg congenital muscular dystrophy;C1836373:Autosomal recessive limb-girdle muscular dystrophy type 2K;C5436962:Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.97

.;.;.;D;.;D

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

D;D;D;D;.;D

MetaRNN

Benign

0.016

T;T;T;T;T;T

MetaSVM

Uncertain

0.77

MutationAssessor

Uncertain

2.4

.;.;.;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-6.5

D;D;D;D;D;D

REVEL

Pathogenic

0.74

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

1.0, 1.0

.;D;.;D;D;.

Vest4

0.62

MVP

0.96

MPC

1.0

ClinPred

0.028

GERP RS

5.0

Varity_R

0.74

gMVP

0.46

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over