9-131506100-GT-GTT

Position:

• chr9-131506100-GT-GTT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001077365.2(POMT1):​c.123-5dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,575,208 control chromosomes in the GnomAD database, including 11,010 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1260 hom., cov: 30)
  • Exomes 𝑓: 0.13 (9750 hom.)
• Consequence: POMT1 NM_001077365.2 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.217

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 9-131506100-G-GT is Benign according to our data. Variant chr9-131506100-G-GT is described in ClinVar as [Likely_benign]. Clinvar id is 95453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMT1	NM_001077365.2	c.123-5dupT		splice_region_variant, intron_variant		ENST00000402686.8	NP_001070833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POMT1	ENST00000402686.8	c.123-5dupT		splice_region_variant, intron_variant		1	NM_001077365.2	ENSP00000385797.4

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17701 AN: 151216 Hom.: 1260 Cov.: 30

Gnomad AFR AF: 0.0623

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.00849

Gnomad SAS AF: 0.0512

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.0385

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.113

GnomAD3 exomes AF: 0.115 AC: 27334 AN: 238246 Hom.: 1510 AF XY: 0.114 AC XY: 14717 AN XY: 129006

Gnomad AFR exome AF: 0.0579

Gnomad AMR exome AF: 0.0655

Gnomad ASJ exome AF: 0.128

Gnomad EAS exome AF: 0.00773

Gnomad SAS exome AF: 0.0535

Gnomad FIN exome AF: 0.229

Gnomad NFE exome AF: 0.150

Gnomad OTH exome AF: 0.116

GnomAD4 exome AF: 0.132 AC: 188049 AN: 1423874 Hom.: 9750 Cov.: 32 AF XY: 0.130 AC XY: 92066 AN XY: 709008

Gnomad4 AFR exome AF: 0.0566

Gnomad4 AMR exome AF: 0.0675

Gnomad4 ASJ exome AF: 0.130

Gnomad4 EAS exome AF: 0.00643

Gnomad4 SAS exome AF: 0.0565

Gnomad4 FIN exome AF: 0.216

Gnomad4 NFE exome AF: 0.145

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.117 AC: 17709 AN: 151334 Hom.: 1260 Cov.: 30 AF XY: 0.120 AC XY: 8865 AN XY: 73900

Gnomad4 AFR AF: 0.0623

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.00851

Gnomad4 SAS AF: 0.0516

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.112

Bravo AF: 0.103

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 17, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 25, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 1457/12518=11.6% -

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

- -

Limb-girdle muscular dystrophy, recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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

- -

Congenital muscular dystrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 01, 2014

The variant is found in CORTICAL-BRAIN panel(s). -

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

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: rs148086540; hg19: chr9-134381487;