rs3739494

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001077365.2(POMT1):c.1047T>C(p.Asp349Asp) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.54

Publications

33 publications found

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 Gene-Disease associations (from GenCC):

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Laboratory for Molecular Medicine, Genomics England PanelApp
myopathy caused by variation in POMT1
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
autosomal recessive limb-girdle muscular dystrophy type 2K
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
congenital muscular dystrophy with cerebellar involvement
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
congenital muscular dystrophy with intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
congenital muscular dystrophy without intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
muscle-eye-brain disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
muscular dystrophy-dystroglycanopathy, type A
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

POMT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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 rank	MANE	Protein	UniProt
POMT1	NM_001077365.2 link	c.1047T>C	p.Asp349Asp	synonymous_variant	Exon 11 of 20	ENST00000402686.8	NP_001070833.1	Q9Y6A1-2A0A140VKE0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMT1	ENST00000402686.8 link	c.1047T>C	p.Asp349Asp	synonymous_variant	Exon 11 of 20	1	NM_001077365.2	ENSP00000385797.4		Q9Y6A1-2

Frequencies

GnomAD3 genomes

AF:

0.888

AC:

134901

AN:

151990

Hom.:

60568

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.924

AC:

232202

AN:

251354

AF XY:

0.932

show subpopulations

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 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.:

AF XY:

0.947

AC XY:

688653

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.732

AC:

24520

AN:

33480

American (AMR)

AF:

0.842

AC:

37654

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.942

AC:

24632

AN:

26136

East Asian (EAS)

AF:

0.916

AC:

36374

AN:

39698

South Asian (SAS)

AF:

0.971

AC:

83704

AN:

86244

European-Finnish (FIN)

AF:

0.976

AC:

52144

AN:

53414

Middle Eastern (MID)

AF:

0.936

AC:

5399

AN:

5768

European-Non Finnish (NFE)

AF:

0.954

AC:

1061248

AN:

1111994

Other (OTH)

AF:

0.928

AC:

56040

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

4992

9983

14975

19966

24958

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.887

AC:

134974

AN:

152108

Hom.:

60599

Cov.:

AF XY:

0.889

AC XY:

66130

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.746

AC:

30904

AN:

41450

American (AMR)

AF:

0.861

AC:

13166

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.941

AC:

3267

AN:

3470

East Asian (EAS)

AF:

0.918

AC:

4732

AN:

5154

South Asian (SAS)

AF:

0.971

AC:

4680

AN:

4822

European-Finnish (FIN)

AF:

0.978

AC:

10373

AN:

10608

Middle Eastern (MID)

AF:

0.915

AC:

269

AN:

294

European-Non Finnish (NFE)

AF:

0.954

AC:

64869

AN:

68002

Other (OTH)

AF:

0.897

AC:

1894

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

701

1402

2103

2804

3505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.930

Hom.:

128788

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

LINK: link

Submissions by phenotype

not specified

Benign:5

Apr 23, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 26, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Autosomal recessive limb-girdle muscular dystrophy type 2K

Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.49

(source)

DANN

Benign

0.67

PhyloP100

-1.5

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

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rs3739494

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over