rs4740164

Positions:

chr9-131511394-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001077365.2(POMT1):c.913G>A(p.Val305Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0467 in 1,614,046 control chromosomes in the GnomAD database, including 2,249 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 243 hom., cov: 33)

Exomes 𝑓: 0.047 ( 2006 hom. )

Consequence

POMT1
NM_001077365.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: 4.94

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=0.0016653538).

BP6

Variant 9-131511394-G-A is Benign according to our data. Variant chr9-131511394-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 95471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-131511394-G-A is described in Lovd as [Benign]. Variant chr9-131511394-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMT1	NM_001077365.2 linkuse as main transcript	c.913G>A	p.Val305Ile	missense_variant	10/20	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.913G>A	p.Val305Ile	missense_variant	10/20	1	NM_001077365.2	ENSP00000385797	P1	Q9Y6A1-2

Frequencies

GnomAD3 genomes

AF:

0.0436

AC:

6632

AN:

152166

Hom.:

244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0170

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.111

Gnomad ASJ

AF:

0.0556

Gnomad EAS

AF:

0.0768

Gnomad SAS

AF:

0.0280

Gnomad FIN

AF:

0.0224

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0450

Gnomad OTH

AF:

0.0551

GnomAD3 exomes

AF:

0.0567

AC:

14271

AN:

251494

Hom.:

634

AF XY:

0.0534

AC XY:

7252

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0170

Gnomad AMR exome

AF:

0.143

Gnomad ASJ exome

AF:

0.0548

Gnomad EAS exome

AF:

0.0813

Gnomad SAS exome

AF:

0.0288

Gnomad FIN exome

AF:

0.0230

Gnomad NFE exome

AF:

0.0461

Gnomad OTH exome

AF:

0.0594

GnomAD4 exome

AF:

0.0470

AC:

68688

AN:

1461762

Hom.:

2006

Cov.:

AF XY:

0.0462

AC XY:

33562

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.0173

Gnomad4 AMR exome

AF:

0.141

Gnomad4 ASJ exome

AF:

0.0547

Gnomad4 EAS exome

AF:

0.0795

Gnomad4 SAS exome

AF:

0.0281

Gnomad4 FIN exome

AF:

0.0238

Gnomad4 NFE exome

AF:

0.0450

Gnomad4 OTH exome

AF:

0.0537

GnomAD4 genome

AF:

0.0435

AC:

6627

AN:

152284

Hom.:

243

Cov.:

AF XY:

0.0440

AC XY:

3278

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0170

Gnomad4 AMR

AF:

0.111

Gnomad4 ASJ

AF:

0.0556

Gnomad4 EAS

AF:

0.0768

Gnomad4 SAS

AF:

0.0278

Gnomad4 FIN

AF:

0.0224

Gnomad4 NFE

AF:

0.0450

Gnomad4 OTH

AF:

0.0540

Alfa

AF:

0.0489

Hom.:

437

Bravo

AF:

0.0514

TwinsUK

AF:

0.0399

AC:

148

ALSPAC

AF:

0.0431

AC:

166

ESP6500AA

AF:

0.0209

AC:

ESP6500EA

AF:

0.0464

AC:

399

ExAC

AF:

0.0533

AC:

6471

Asia WGS

AF:

0.0580

AC:

203

AN:

3478

EpiCase

AF:

0.0496

EpiControl

AF:

0.0513

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 02, 2012	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jan 13, 2015	p.Val327Ile in exon 10 of POMT1: This variant is not expected to have clinical s ignificance because it has been identified in 4.6% (399/8600) of European Americ an chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.e du/EVS/; dbSNP rs4740164). -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Autosomal recessive limb-girdle muscular dystrophy type 2K

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Oct 25, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Autosomal recessive limb-girdle muscular dystrophy type 2K;C4284790:Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1;C5436962:Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Apr 14, 2017

- -

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

- -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.22

DEOGEN2

Benign

0.045

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.27

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.99

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

PROVEAN

Benign

-0.71

REVEL

Benign

0.24

Sift

Benign

0.86

Sift4G

Benign

0.24

ClinPred

0.016

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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