rs12115566

Positions:

chr9-131522077-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000402686.8(POMT1):c.1856C>T(p.Ala619Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00491 in 1,614,056 control chromosomes in the GnomAD database, including 107 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A619A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.015 ( 59 hom., cov: 33)

Exomes 𝑓: 0.0038 ( 48 hom. )

Consequence

POMT1
ENST00000402686.8 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.797

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:

(HGNC:):

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=0.0031572282).

BP6

Variant 9-131522077-C-T is Benign according to our data. Variant chr9-131522077-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 130011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-131522077-C-T is described in Lovd as [Likely_benign]. Variant chr9-131522077-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0154 (2352/152268) while in subpopulation AFR AF= 0.0477 (1983/41540). AF 95% confidence interval is 0.046. There are 59 homozygotes in gnomad4. There are 1138 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 59 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMT1	NM_001077365.2 linkuse as main transcript	c.1856C>T	p.Ala619Val	missense_variant	19/20	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.1856C>T	p.Ala619Val	missense_variant	19/20	1	NM_001077365.2	ENSP00000385797	P1	Q9Y6A1-2
	ENST00000415423.1 linkuse as main transcript	n.62+91G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

2343

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0476

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.00606

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00828

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00273

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.00665

AC:

1671

AN:

251270

Hom.:

AF XY:

0.00628

AC XY:

853

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.0489

Gnomad AMR exome

AF:

0.00477

Gnomad ASJ exome

AF:

0.00447

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00787

Gnomad FIN exome

AF:

0.000603

Gnomad NFE exome

AF:

0.00335

Gnomad OTH exome

AF:

0.00505

GnomAD4 exome

AF:

0.00381

AC:

5571

AN:

1461788

Hom.:

Cov.:

AF XY:

0.00393

AC XY:

2861

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.0476

Gnomad4 AMR exome

AF:

0.00501

Gnomad4 ASJ exome

AF:

0.00440

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00813

Gnomad4 FIN exome

AF:

0.000900

Gnomad4 NFE exome

AF:

0.00218

Gnomad4 OTH exome

AF:

0.00662

GnomAD4 genome

AF:

0.0154

AC:

2352

AN:

152268

Hom.:

Cov.:

AF XY:

0.0153

AC XY:

1138

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0477

Gnomad4 AMR

AF:

0.00529

Gnomad4 ASJ

AF:

0.00606

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00787

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00273

Gnomad4 OTH

AF:

0.0157

Alfa

AF:

0.00531

Hom.:

Bravo

AF:

0.0168

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.0415

AC:

183

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.00757

AC:

919

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.00431

EpiControl

AF:

0.00379

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 01, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -

Autosomal recessive limb-girdle muscular dystrophy type 2K

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

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

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.34

CADD

Benign

6.2

DANN

Benign

0.93

DEOGEN2

Uncertain

0.64

.;.;.;D;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.39

T;T;T;T;.;T

MetaRNN

Benign

0.0032

T;T;T;T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

1.4

.;.;.;L;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.93

N;N;N;N;N;N

REVEL

Benign

0.18

Sift

Benign

0.32

T;T;T;T;T;T

Sift4G

Benign

0.29

T;T;T;T;T;T

Polyphen

0.012, 0.032

.;B;.;B;B;.

Vest4

0.19

MVP

0.82

MPC

0.25

ClinPred

0.0026

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.022

gMVP

0.22

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