9-131511357-T-C

Position:

chr9-131511357-T-C

Variant summary

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

The NM_001374689.1(POMT1):c.859T>C(p.Ser287Pro) 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 1,613,692 control chromosomes in the GnomAD database, including 714,864 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict 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_001374689.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.67

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:

POMT1 (HGNC:):

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=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. Variant chr9-131511357-T-C 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/exons	MANE	Protein	UniProt
POMT1	NM_001077365.2 linkuse as main transcript	c.876T>C	p.Thr292Thr	synonymous_variant	10/20	ENST00000402686.8	NP_001070833.1	Q9Y6A1-2A0A140VKE0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POMT1	ENST00000402686.8 linkuse as main transcript	c.876T>C	p.Thr292Thr	synonymous_variant	10/20	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

GnomAD3 exomes

AF:

0.924

AC:

232276

AN:

251438

Hom.:

107858

AF XY:

0.932

AC XY:

126689

AN XY:

135888

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 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:

1381478

AN:

1461530

Hom.:

654239

Cov.:

AF XY:

0.947

AC XY:

688522

AN XY:

727046

show subpopulations

Gnomad4 AFR exome

AF:

0.733

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:

135030

AN:

152162

Hom.:

60625

Cov.:

AF XY:

0.889

AC XY:

66157

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.746

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:

0.897

Alfa

AF:

0.922

Hom.:

42437

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

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 23, 2013	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 26, 2014	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. -

Autosomal recessive limb-girdle muscular dystrophy type 2K

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

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

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

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

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

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.35

Sift

Uncertain

0.014

Sift4G

Benign

0.33

ClinPred

0.0064

GERP RS

0.21

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