Variant rs59515295 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001077365.2(POMT1):c.1082+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,612,492 control chromosomes in the GnomAD database, including 15,303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1611 hom., cov: 31)

Exomes 𝑓: 0.13 ( 13692 hom. )

Consequence

POMT1
NM_001077365.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 1.08

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 (BayesDel_noAF=-0.78).

BP6

Variant 9-131512152-G-A is Benign according to our data. Variant chr9-131512152-G-A is described in ClinVar as [Benign]. Clinvar id is 95451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-131512152-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 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.1082+16G>A		intron_variant		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.1082+16G>A		intron_variant		1	NM_001077365.2	ENSP00000385797.4		Q9Y6A1-2

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

21050

AN:

152006

Hom.:

1610

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0486

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.146

Gnomad OTH

AF:

0.130

GnomAD3 exomes

AF:

0.116

AC:

28784

AN:

248402

Hom.:

2012

AF XY:

0.113

AC XY:

15229

AN XY:

134290

show subpopulations

Gnomad AFR exome

AF:

0.151

Gnomad AMR exome

AF:

0.0666

Gnomad ASJ exome

AF:

0.129

Gnomad EAS exome

AF:

0.000273

Gnomad SAS exome

AF:

0.0499

Gnomad FIN exome

AF:

0.200

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.131

AC:

191590

AN:

1460368

Hom.:

13692

Cov.:

AF XY:

0.129

AC XY:

93525

AN XY:

726334

show subpopulations

Gnomad4 AFR exome

AF:

0.149

Gnomad4 AMR exome

AF:

0.0696

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.000328

Gnomad4 SAS exome

AF:

0.0537

Gnomad4 FIN exome

AF:

0.201

Gnomad4 NFE exome

AF:

0.141

Gnomad4 OTH exome

AF:

0.122

GnomAD4 genome

AF:

0.138

AC:

21062

AN:

152124

Hom.:

1611

Cov.:

AF XY:

0.139

AC XY:

10359

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.154

Gnomad4 AMR

AF:

0.108

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0488

Gnomad4 FIN

AF:

0.192

Gnomad4 NFE

AF:

0.146

Gnomad4 OTH

AF:

0.128

Alfa

AF:

0.146

Hom.:

494

Bravo

AF:

0.130

Asia WGS

AF:

0.0330

AC:

117

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
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)	Jul 24, 2012	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 19, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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_noAF

Benign

-0.78

CADD

Benign

2.2

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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