9-131511357-T-C

Variant names:

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.876T>C(p.Thr292Thr) 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 1,613,692 control chromosomes in the GnomAD database, including 714,864 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.89 ( 60625 hom., cov: 31)

Exomes 𝑓: 0.95 ( 654239 hom. )

Consequence

POMT1
NM_001077365.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.67

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 (MetaRNN=8.0885815E-7).

BP6

Variant 9-131511357-T-C is Benign according to our data. Variant chr9-131511357-T-C is described in ClinVar as [Benign]. Clinvar id is 167519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.67 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.876T>C	p.Thr292Thr	synonymous_variant	Exon 10 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.876T>C	p.Thr292Thr	synonymous_variant	Exon 10 of 20	1	NM_001077365.2	ENSP00000385797.4		Q9Y6A1-2

Frequencies

GnomAD3 genomes

AF:

0.888

AC:

134957

AN:

152044

Hom.:

60594

Cov.:

show subpopulations

Gnomad AFR

AF:

0.746

Gnomad AMI

AF:

0.899

Gnomad AMR

AF:

0.861

Gnomad ASJ

AF:

0.942

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:

232276

AN:

251438

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:

1381478

AN:

1461530

Hom.:

654239

Cov.:

AF XY:

0.947

AC XY:

688522

AN XY:

727046

show subpopulations

African (AFR)

AF:

0.733

AC:

24514

AN:

33466

American (AMR)

AF:

0.842

AC:

37663

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.942

AC:

24632

AN:

26136

East Asian (EAS)

AF:

0.916

AC:

36369

AN:

39686

South Asian (SAS)

AF:

0.971

AC:

83715

AN:

86254

European-Finnish (FIN)

AF:

0.976

AC:

52148

AN:

53418

Middle Eastern (MID)

AF:

0.936

AC:

5393

AN:

5762

European-Non Finnish (NFE)

AF:

0.954

AC:

1061016

AN:

1111720

Other (OTH)

AF:

0.928

AC:

56028

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

4178

8356

12535

16713

20891

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.887

AC:

135030

AN:

152162

Hom.:

60625

Cov.:

AF XY:

0.889

AC XY:

66157

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.746

AC:

30922

AN:

41456

American (AMR)

AF:

0.861

AC:

13165

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.942

AC:

3269

AN:

3472

East Asian (EAS)

AF:

0.918

AC:

4746

AN:

5172

South Asian (SAS)

AF:

0.971

AC:

4683

AN:

4824

European-Finnish (FIN)

AF:

0.978

AC:

10368

AN:

10606

Middle Eastern (MID)

AF:

0.915

AC:

269

AN:

294

European-Non Finnish (NFE)

AF:

0.954

AC:

64891

AN:

68026

Other (OTH)

AF:

0.897

AC:

1897

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

697

1393

2090

2786

3483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.924

Hom.:

134745

Bravo

AF:

0.869

TwinsUK

AF:

0.960

AC:

3559

ALSPAC

AF:

0.955

AC:

3682

ESP6500AA

AF:

0.741

AC:

3263

ESP6500EA

AF:

0.952

AC:

8189

ExAC

AF:

0.923

AC:

112067

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

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.942T) is the minor allele. This al lele (T) has been identified in 4.8% (411/8598) of European American chromosomes and 26% (1143/4406) of African American chromosomes by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS/; dbSNP rs10901065) and thus meets criteria to be classified as benign. -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 23, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

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_addAF

Benign

-0.26

BayesDel_noAF

Uncertain

0.0

CADD

Benign

1.7

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.048

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.15

MetaRNN

Benign

8.1e-7

MetaSVM

Benign

-0.98

PhyloP100

-1.7

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.35

Sift

Uncertain

0.014

Sift4G

Benign

0.33

ClinPred

0.0064

GERP RS

0.21

Mutation Taster

=100/0

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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9-131511357-T-C

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