rs144051476

Positions:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1

The ENST00000402686.8(POMT1):c.2168G>A(p.Arg723Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000307 in 1,610,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

POMT1
ENST00000402686.8 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 6.57

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 -14 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008366883).

BP6

Variant 9-131523096-G-A is Benign according to our data. Variant chr9-131523096-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 130012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-131523096-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00146 (223/152306) while in subpopulation AFR AF= 0.00488 (203/41568). AF 95% confidence interval is 0.00433. There are 0 homozygotes in gnomad4. There are 114 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMT1	NM_001077365.2 linkuse as main transcript	c.2168G>A	p.Arg723Gln	missense_variant	20/20	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.2168G>A	p.Arg723Gln	missense_variant	20/20	1	NM_001077365.2	ENSP00000385797	P1	Q9Y6A1-2

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

223

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00490

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000981

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000495

AC:

123

AN:

248426

Hom.:

AF XY:

0.000350

AC XY:

AN XY:

134402

show subpopulations

Gnomad AFR exome

AF:

0.00563

Gnomad AMR exome

AF:

0.000639

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000797

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000186

AC:

272

AN:

1458458

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

109

AN XY:

725438

show subpopulations

Gnomad4 AFR exome

AF:

0.00413

Gnomad4 AMR exome

AF:

0.000628

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000774

Gnomad4 OTH exome

AF:

0.000299

GnomAD4 genome

AF:

0.00146

AC:

223

AN:

152306

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

114

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00488

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000223

Hom.:

Bravo

AF:

0.00175

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000503

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 24, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 14, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 20, 2014	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Dec 02, 2015	- -

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

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

POMT1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 25, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.21

.;.;.;T;.;T

Eigen

Benign

0.099

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.88

D;D;D;D;.;D

MetaRNN

Benign

0.0084

T;T;T;T;T;T

MetaSVM

Uncertain

-0.16

MutationAssessor

Benign

1.4

.;.;.;L;.;.

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.73

N;N;N;N;N;N

REVEL

Uncertain

0.42

Sift

Benign

0.25

T;T;T;T;T;T

Sift4G

Benign

0.47

T;T;T;T;T;T

Polyphen

0.78, 0.96

.;P;.;D;P;.

Vest4

0.36

MVP

0.93

MPC

0.72

ClinPred

0.024

GERP RS

4.0

Varity_R

0.14

gMVP

0.56

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