Genetic Variant POMT1:c.123-5dupT (chr9-131506100-G-GT) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

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

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.217

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
POMT1	NM_001077365.2 link	c.123-5dupT		splice_region_variant, intron_variant	Intron 2 of 19	ENST00000402686.8	NP_001070833.1	Q9Y6A1-2A0A140VKE0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMT1	ENST00000402686.8 link	c.123-5dupT		splice_region_variant, intron_variant	Intron 2 of 19	1	NM_001077365.2	ENSP00000385797.4		Q9Y6A1-2

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17701

AN:

151216

Hom.:

1260

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.130

AC XY:

92066

AN XY:

709008

show subpopulations

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.:

AF XY:

0.120

AC XY:

8865

AN XY:

73900

show subpopulations

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

LINK: link

Submissions by phenotype

not specified

Benign:2

Dec 17, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 25, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1

Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Limb-girdle muscular dystrophy, recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital muscular dystrophy

Benign:1

Apr 01, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1

Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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