rs4740165

Variant summary

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

The NM_001077365.2(POMT1):c.2003+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.922 in 1,612,548 control chromosomes in the GnomAD database, including 689,255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 55947 hom., cov: 33)

Exomes 𝑓: 0.93 ( 633308 hom. )

Consequence

POMT1
NM_001077365.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -1.60

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 (BayesDel_noAF=-0.89).

BP6

Variant 9-131522237-C-T is Benign according to our data. Variant chr9-131522237-C-T is described in ClinVar as [Benign]. Clinvar id is 95460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-131522237-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMT1	NM_001077365.2 linkuse as main transcript	c.2003+13C>T		intron_variant		ENST00000402686.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMT1	ENST00000402686.8 linkuse as main transcript	c.2003+13C>T		intron_variant		1	NM_001077365.2	P1	Q9Y6A1-2
	ENST00000415423.1 linkuse as main transcript			upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.848

AC:

128966

AN:

152100

Hom.:

55928

Cov.:

show subpopulations

Gnomad AFR

AF:

0.648

Gnomad AMI

AF:

0.897

Gnomad AMR

AF:

0.846

Gnomad ASJ

AF:

0.923

Gnomad EAS

AF:

0.917

Gnomad SAS

AF:

0.962

Gnomad FIN

AF:

0.934

Gnomad MID

AF:

0.873

Gnomad NFE

AF:

0.938

Gnomad OTH

AF:

0.864

GnomAD3 exomes

AF:

0.902

AC:

225334

AN:

249940

Hom.:

102434

AF XY:

0.912

AC XY:

123463

AN XY:

135376

show subpopulations

Gnomad AFR exome

AF:

0.636

Gnomad AMR exome

AF:

0.829

Gnomad ASJ exome

AF:

0.925

Gnomad EAS exome

AF:

0.914

Gnomad SAS exome

AF:

0.961

Gnomad FIN exome

AF:

0.932

Gnomad NFE exome

AF:

0.935

Gnomad OTH exome

AF:

0.913

GnomAD4 exome

AF:

0.930

AC:

1357755

AN:

1460330

Hom.:

633308

Cov.:

AF XY:

0.932

AC XY:

676988

AN XY:

726600

show subpopulations

Gnomad4 AFR exome

AF:

0.633

Gnomad4 AMR exome

AF:

0.830

Gnomad4 ASJ exome

AF:

0.925

Gnomad4 EAS exome

AF:

0.916

Gnomad4 SAS exome

AF:

0.962

Gnomad4 FIN exome

AF:

0.931

Gnomad4 NFE exome

AF:

0.942

Gnomad4 OTH exome

AF:

0.909

GnomAD4 genome

AF:

0.848

AC:

129020

AN:

152218

Hom.:

55947

Cov.:

AF XY:

0.850

AC XY:

63258

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.647

Gnomad4 AMR

AF:

0.846

Gnomad4 ASJ

AF:

0.923

Gnomad4 EAS

AF:

0.917

Gnomad4 SAS

AF:

0.962

Gnomad4 FIN

AF:

0.934

Gnomad4 NFE

AF:

0.938

Gnomad4 OTH

AF:

0.865

Alfa

AF:

0.915

Hom.:

59029

Bravo

AF:

0.829

Asia WGS

AF:

0.890

AC:

3092

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

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, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 23, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jan 13, 2015	c.2069+13C>T in intron 19 of POMT1: This variant is not expected to have clinica l significance because it is not located within the conserved splice consensus s equence. It has been identified in 35.2% (1549/4406) of African American chromos omes from a broad population by the NHLBI Exome Sequencing Project (http://evs.g s.washington.edu/EVS; dbSNP rs4740165). -
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	-	- -

Autosomal recessive limb-girdle muscular dystrophy type 2K

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
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

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

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

-0.89

Cadd

Benign

1.0

Dann

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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