rs2277152

Positions:

• chr9-131520241-C-G

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.1698+48C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.921 in 1,494,726 control chromosomes in the GnomAD database, including 637,871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (55948 hom., cov: 32)
  • Exomes 𝑓: 0.93 (581923 hom.)
• Consequence: POMT1 NM_001077365.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.168

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 9-131520241-C-G is Benign according to our data. Variant chr9-131520241-C-G is described in ClinVar as [Benign]. Clinvar id is 260142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-131520241-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMT1	NM_001077365.2	c.1698+48C>G		intron_variant		ENST00000402686.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMT1	ENST00000402686.8	c.1698+48C>G		intron_variant		1	NM_001077365.2	P1
	ENST00000415423.1	n.62+1927G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128973 AN: 152094 Hom.: 55929 Cov.: 32

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.922

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.962

Gnomad FIN AF: 0.935

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.938

Gnomad OTH AF: 0.864

GnomAD3 exomes AF: 0.902 AC: 220470 AN: 244392 Hom.: 100218 AF XY: 0.912 AC XY: 121352 AN XY: 132990

Gnomad AFR exome AF: 0.636

Gnomad AMR exome AF: 0.829

Gnomad ASJ exome AF: 0.925

Gnomad EAS exome AF: 0.915

Gnomad SAS exome AF: 0.961

Gnomad FIN exome AF: 0.931

Gnomad NFE exome AF: 0.936

Gnomad OTH exome AF: 0.913

GnomAD4 exome AF: 0.930 AC: 1247875 AN: 1342514 Hom.: 581923 Cov.: 19 AF XY: 0.932 AC XY: 628289 AN XY: 674356

Gnomad4 AFR exome AF: 0.636

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: 0.930

Gnomad4 NFE exome AF: 0.942

Gnomad4 OTH exome AF: 0.909

GnomAD4 genome AF: 0.848 AC: 129027 AN: 152212 Hom.: 55948 Cov.: 32 AF XY: 0.850 AC XY: 63257 AN XY: 74424

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.846

Gnomad4 ASJ AF: 0.922

Gnomad4 EAS AF: 0.917

Gnomad4 SAS AF: 0.963

Gnomad4 FIN AF: 0.935

Gnomad4 NFE AF: 0.938

Gnomad4 OTH AF: 0.865

Alfa AF: 0.891 Hom.: 11237

Bravo AF: 0.829

Asia WGS AF: 0.890 AC: 3094 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

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

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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. -

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	-0.85
CADD	Benign	2.2
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2277152; hg19: chr9-134395628;