Variant 9-131522955-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001077365.2(POMT1):c.2027T>C(p.Phe676Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000415 in 1,445,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

POMT1
NM_001077365.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.32

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.755

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMT1	NM_001077365.2 linkuse as main transcript	c.2027T>C	p.Phe676Ser	missense_variant	20/20	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.2027T>C	p.Phe676Ser	missense_variant	20/20	1	NM_001077365.2	ENSP00000385797.4		Q9Y6A1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000175

AC:

AN:

229042

Hom.:

AF XY:

0.0000161

AC XY:

AN XY:

123868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000171

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000174

GnomAD4 exome

AF:

0.00000415

AC:

AN:

1445394

Hom.:

Cov.:

AF XY:

0.00000418

AC XY:

AN XY:

717876

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000127

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Walker-Warburg congenital muscular dystrophy;C1836373:Autosomal recessive limb-girdle muscular dystrophy type 2K;C5436962:Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 18, 2022

This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 698 of the POMT1 protein (p.Phe698Ser). This variant is present in population databases (no rsID available, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with POMT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 538721). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Uncertain

0.093

BayesDel_noAF

Pathogenic

0.17

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.86

.;.;.;D;.;D

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.020

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.83

T;T;T;T;.;T

M_CAP

Uncertain

0.091

MetaRNN

Pathogenic

0.75

D;D;D;D;D;D

MetaSVM

Uncertain

0.30

MutationAssessor

Uncertain

2.0

.;.;.;M;.;.

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-4.6

D;D;D;D;D;D

REVEL

Uncertain

0.61

Sift

Uncertain

0.0020

D;D;D;D;D;D

Sift4G

Uncertain

0.0040

D;D;D;D;D;D

Polyphen

0.016, 0.031

.;B;.;B;B;.

Vest4

0.62

MutPred

0.59

.;.;.;Gain of disorder (P = 0.0046);.;.;

MVP

0.92

MPC

0.72

ClinPred

0.83

GERP RS

5.3

Varity_R

0.73

gMVP

0.58

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