ENST00000372228.9:c.752A>G

Variant names:

Variant summary

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

The ENST00000372228.9(POMT1):c.752A>G(p.Gln251Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.94 in 1,614,106 control chromosomes in the GnomAD database, including 714,950 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q251W) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.89 ( 60620 hom., cov: 33)

Exomes 𝑓: 0.95 ( 654330 hom. )

Consequence

POMT1
ENST00000372228.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.989

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=2.4782473E-6).

BP6

Variant 9-131510049-A-G is Benign according to our data. Variant chr9-131510049-A-G is described in ClinVar as [Benign]. Clinvar id is 227021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-131510049-A-G is described in Lovd as [Benign].

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.699+53A>G		intron_variant	Intron 8 of 19	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.699+53A>G		intron_variant	Intron 8 of 19	1	NM_001077365.2	ENSP00000385797.4		Q9Y6A1-2

Frequencies

GnomAD3 genomes

AF:

0.887

AC:

134972

AN:

152110

Hom.:

60591

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

GnomAD3 exomes

AF:

0.924

AC:

231971

AN:

251126

Hom.:

107708

AF XY:

0.932

AC XY:

126534

AN XY:

135722

show subpopulations

Gnomad AFR exome

AF:

0.734

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:

1381729

AN:

1461878

Hom.:

654330

Cov.:

AF XY:

0.947

AC XY:

688666

AN XY:

727236

show subpopulations

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:

135043

AN:

152228

Hom.:

60620

Cov.:

AF XY:

0.889

AC XY:

66184

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.745

Gnomad4 AMR

AF:

0.861

Gnomad4 ASJ

AF:

0.942

Gnomad4 EAS

AF:

0.918

Gnomad4 SAS

AF:

0.971

Gnomad4 FIN

AF:

0.978

Gnomad4 NFE

AF:

0.954

Gnomad4 OTH

AF:

0.895

Alfa

AF:

0.940

Hom.:

170709

Bravo

AF:

0.869

TwinsUK

AF:

0.960

AC:

3559

ALSPAC

AF:

0.955

AC:

3682

ESP6500AA

AF:

0.738

AC:

3253

ESP6500EA

AF:

0.952

AC:

8183

ExAC

AF:

0.923

AC:

112055

Asia WGS

AF:

0.910

AC:

3164

AN:

3478

EpiCase

AF:

0.949

EpiControl

AF:

0.947

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

- -

Dec 11, 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.752A) is the minor allele. This al lele (A) has been identified in 5% (417/8600) of European American chromosomes a nd 26% (1153/4406) of African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs2296949). -

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

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

CADD

Benign

1.8

DANN

Benign

0.16

DEOGEN2

Benign

0.17

T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00028

LIST_S2

Benign

0.13

T;T;T

MetaRNN

Benign

0.0000025

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

.;N;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.080

N;N;N

REVEL

Benign

0.20

Sift

Benign

0.61

T;T;T

Sift4G

Benign

0.50

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.0080

MPC

0.26

ClinPred

0.00016

GERP RS

1.3

Varity_R

0.014

gMVP

0.052

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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