rs59515295

Positions:

• chr9-131512152-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 1.08

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]

ACMG classification

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	UniProt
POMT1	NM_001077365.2	c.1082+16G>A		intron_variant		ENST00000402686.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMT1	ENST00000402686.8	c.1082+16G>A		intron_variant		1	NM_001077365.2	P1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21050 AN: 152006 Hom.: 1610 Cov.: 31

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

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.: 36 AF XY: 0.129 AC XY: 93525 AN XY: 726334

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.: 31 AF XY: 0.139 AC XY: 10359 AN XY: 74396

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:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 24, 2012	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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: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

Invitae

Feb 01, 2024

- -

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

Other links and lift over

dbSNP: rs59515295; hg19: chr9-134387539; COSMIC: COSV61225183; COSMIC: COSV61225183;