rs34954751

chr9-131520187-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001077365.2(POMT1):c.1692G>A(p.Arg564=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0283 in 1,612,506 control chromosomes in the GnomAD database, including 773 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (55 hom., cov: 32)
  • Exomes 𝑓: 0.029 (718 hom.)
• Consequence: POMT1 NM_001077365.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.111

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 9-131520187-G-A is Benign according to our data. Variant chr9-131520187-G-A is described in ClinVar as [Benign]. Clinvar id is 130008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-131520187-G-A is described in Lovd as [Benign]. Variant chr9-131520187-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.111 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0217 (3302/152286) while in subpopulation NFE AF= 0.0309 (2105/68018). AF 95% confidence interval is 0.0298. There are 55 homozygotes in gnomad4. There are 1620 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 55 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMT1	NM_001077365.2	c.1692G>A	p.Arg564=	synonymous_variant	17/20	ENST00000402686.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMT1	ENST00000402686.8	c.1692G>A	p.Arg564=	synonymous_variant	17/20	1	NM_001077365.2	P1
	ENST00000415423.1	n.62+1981C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0217 AC: 3302 AN: 152168 Hom.: 55 Cov.: 32

Gnomad AFR AF: 0.00541

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0209

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00807

Gnomad FIN AF: 0.0487

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0309

Gnomad OTH AF: 0.0287

GnomAD3 exomes AF: 0.0228 AC: 5711 AN: 250686 Hom.: 87 AF XY: 0.0232 AC XY: 3147 AN XY: 135654

Gnomad AFR exome AF: 0.00513

Gnomad AMR exome AF: 0.0159

Gnomad ASJ exome AF: 0.00537

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00947

Gnomad FIN exome AF: 0.0484

Gnomad NFE exome AF: 0.0312

Gnomad OTH exome AF: 0.0251

GnomAD4 exome AF: 0.0290 AC: 42327 AN: 1460220 Hom.: 718 Cov.: 32 AF XY: 0.0285 AC XY: 20671 AN XY: 726468

Gnomad4 AFR exome AF: 0.00502

Gnomad4 AMR exome AF: 0.0172

Gnomad4 ASJ exome AF: 0.00635

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0102

Gnomad4 FIN exome AF: 0.0470

Gnomad4 NFE exome AF: 0.0326

Gnomad4 OTH exome AF: 0.0250

GnomAD4 genome AF: 0.0217 AC: 3302 AN: 152286 Hom.: 55 Cov.: 32 AF XY: 0.0218 AC XY: 1620 AN XY: 74450

Gnomad4 AFR AF: 0.00539

Gnomad4 AMR AF: 0.0210

Gnomad4 ASJ AF: 0.00547

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00807

Gnomad4 FIN AF: 0.0487

Gnomad4 NFE AF: 0.0309

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0248 Hom.: 43

Bravo AF: 0.0197

Asia WGS AF: 0.00346 AC: 13 AN: 3478

EpiCase AF: 0.0329

EpiControl AF: 0.0333

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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	Jan 13, 2015	p.Arg586Arg in exon 17 of POMT1: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 3.4% (291/8600) o f European American chromosomes by the NHLBI Exome Sequencing Project (http://ev s.gs.washington.edu/EVS/; dbSNP rs34954751). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 21, 2014	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. -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not provided Benign:2

Likely 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	Athena Diagnostics	Aug 28, 2017	- -

Autosomal recessive limb-girdle muscular dystrophy type 2K Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

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

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	6.3
Dann	Benign	0.79

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

Other links and lift over

dbSNP: rs34954751; hg19: chr9-134395574;