rs3739494

Positions:

• chr9-131512101-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001077365.2(POMT1):​c.1047T>C​(p.Asp349=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.94 in 1,613,944 control chromosomes in the GnomAD database, including 714,925 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (60599 hom., cov: 31)
  • Exomes 𝑓: 0.95 (654326 hom.)
• Consequence: POMT1 NM_001077365.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -1.54

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 9-131512101-T-C is Benign according to our data. Variant chr9-131512101-T-C is described in ClinVar as [Benign]. Clinvar id is 167520.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-131512101-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.54 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMT1	NM_001077365.2	c.1047T>C	p.Asp349=	synonymous_variant	11/20	ENST00000402686.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMT1	ENST00000402686.8	c.1047T>C	p.Asp349=	synonymous_variant	11/20	1	NM_001077365.2	P1

Frequencies

GnomAD3 genomes AF: 0.888 AC: 134901 AN: 151990 Hom.: 60568 Cov.: 31

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.899

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.970

Gnomad FIN AF: 0.978

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.954

Gnomad OTH AF: 0.895

GnomAD3 exomes AF: 0.924 AC: 232202 AN: 251354 Hom.: 107825 AF XY: 0.932 AC XY: 126656 AN XY: 135844

Gnomad AFR exome AF: 0.735

Gnomad AMR exome AF: 0.841

Gnomad ASJ exome AF: 0.943

Gnomad EAS exome AF: 0.914

Gnomad SAS exome AF: 0.970

Gnomad FIN exome AF: 0.977

Gnomad NFE exome AF: 0.953

Gnomad OTH exome AF: 0.931

GnomAD4 exome AF: 0.945 AC: 1381715 AN: 1461836 Hom.: 654326 Cov.: 94 AF XY: 0.947 AC XY: 688653 AN XY: 727208

Gnomad4 AFR exome AF: 0.732

Gnomad4 AMR exome AF: 0.842

Gnomad4 ASJ exome AF: 0.942

Gnomad4 EAS exome AF: 0.916

Gnomad4 SAS exome AF: 0.971

Gnomad4 FIN exome AF: 0.976

Gnomad4 NFE exome AF: 0.954

Gnomad4 OTH exome AF: 0.928

GnomAD4 genome AF: 0.887 AC: 134974 AN: 152108 Hom.: 60599 Cov.: 31 AF XY: 0.889 AC XY: 66130 AN XY: 74372

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.861

Gnomad4 ASJ AF: 0.941

Gnomad4 EAS AF: 0.918

Gnomad4 SAS AF: 0.971

Gnomad4 FIN AF: 0.978

Gnomad4 NFE AF: 0.954

Gnomad4 OTH AF: 0.897

Alfa AF: 0.936 Hom.: 106961

Bravo AF: 0.869

Asia WGS AF: 0.917 AC: 3189 AN: 3478

EpiCase AF: 0.949

EpiControl AF: 0.947

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 26, 2014	This is a RefSeq error. The reference base (c.1113T) is the minor allele. This a llele (T) has been identified in 5% (411/8600) of European American chromosomes and 26% (1143/4406) of African American chromosomes by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS/; dbSNP rs3739494) and thus meets cr iteria to be classified as benign. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 23, 2013	- -

Autosomal recessive limb-girdle muscular dystrophy type 2K Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

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

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.49
DANN	Benign	0.67

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: rs3739494; hg19: chr9-134387488;