Variant 9-131513331-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5

The NM_001077365.2(POMT1):c.1175C>T(p.Thr392Met) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000411 in 1,458,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

POMT1
NM_001077365.2 missense, splice_region

Scores

Splicing: ADA: 0.9902

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.42

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 Likely_pathogenic. Variant got 9 ACMG points.

PM1

In a domain MIR 2 (size 57) in uniprot entity POMT1_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_001077365.2

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.956

PP5

Variant 9-131513331-C-T is Pathogenic according to our data. Variant chr9-131513331-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 39435.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMT1	NM_001077365.2 linkuse as main transcript	c.1175C>T	p.Thr392Met	missense_variant, splice_region_variant	12/20	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.1175C>T	p.Thr392Met	missense_variant, splice_region_variant	12/20	1	NM_001077365.2	ENSP00000385797	P1	Q9Y6A1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000820

AC:

AN:

244026

Hom.:

AF XY:

0.00000755

AC XY:

AN XY:

132498

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000912

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1458624

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725598

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000196

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type 2K

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 01, 2012

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.89

.;.;.;D;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.99

D;D;D;D;.

M_CAP

Pathogenic

0.43

MetaRNN

Pathogenic

0.96

D;D;D;D;D

MetaSVM

Pathogenic

0.83

MutationAssessor

Pathogenic

2.9

.;.;.;M;.

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.0

D;D;D;D;D

REVEL

Pathogenic

0.85

Sift

Uncertain

0.0010

D;D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D;D

Polyphen

0.90, 1.0

.;P;.;D;P

Vest4

0.83

MutPred

0.81

.;.;.;Loss of glycosylation at T414 (P = 0.0434);.;

MVP

0.95

MPC

0.91

ClinPred

0.97

GERP RS

5.1

Varity_R

0.83

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Benign

0.67

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