9-131523147-T-C

Position:

• chr9-131523147-T-C

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.*41T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.939 in 1,599,024 control chromosomes in the GnomAD database, including 707,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (60506 hom., cov: 32)
  • Exomes 𝑓: 0.94 (646922 hom.)
• Consequence: POMT1 NM_001077365.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.67

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 9-131523147-T-C is Benign according to our data. Variant chr9-131523147-T-C is described in ClinVar as [Benign]. Clinvar id is 260136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-131523147-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMT1	NM_001077365.2	c.*41T>C		3_prime_UTR_variant	20/20	ENST00000402686.8	NP_001070833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POMT1	ENST00000402686.8	c.*41T>C		3_prime_UTR_variant	20/20	1	NM_001077365.2	ENSP00000385797.4

Frequencies

GnomAD3 genomes AF: 0.887 AC: 134822 AN: 152056 Hom.: 60474 Cov.: 32

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.899

Gnomad AMR AF: 0.860

Gnomad ASJ AF: 0.942

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.970

Gnomad FIN AF: 0.977

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.953

Gnomad OTH AF: 0.895

GnomAD3 exomes AF: 0.923 AC: 217286 AN: 235412 Hom.: 100775 AF XY: 0.932 AC XY: 119096 AN XY: 127798

Gnomad AFR exome AF: 0.732

Gnomad AMR exome AF: 0.841

Gnomad ASJ exome AF: 0.943

Gnomad EAS exome AF: 0.916

Gnomad SAS exome AF: 0.970

Gnomad FIN exome AF: 0.978

Gnomad NFE exome AF: 0.953

Gnomad OTH exome AF: 0.932

GnomAD4 exome AF: 0.945 AC: 1366829 AN: 1446850 Hom.: 646922 Cov.: 42 AF XY: 0.947 AC XY: 680854 AN XY: 719312

Gnomad4 AFR exome AF: 0.731

Gnomad4 AMR exome AF: 0.841

Gnomad4 ASJ exome AF: 0.943

Gnomad4 EAS exome AF: 0.918

Gnomad4 SAS exome AF: 0.970

Gnomad4 FIN exome AF: 0.976

Gnomad4 NFE exome AF: 0.954

Gnomad4 OTH exome AF: 0.928

GnomAD4 genome AF: 0.886 AC: 134896 AN: 152174 Hom.: 60506 Cov.: 32 AF XY: 0.888 AC XY: 66101 AN XY: 74398

Gnomad4 AFR AF: 0.743

Gnomad4 AMR AF: 0.861

Gnomad4 ASJ AF: 0.942

Gnomad4 EAS AF: 0.920

Gnomad4 SAS AF: 0.971

Gnomad4 FIN AF: 0.977

Gnomad4 NFE AF: 0.953

Gnomad4 OTH AF: 0.897

Alfa AF: 0.934 Hom.: 68210

Bravo AF: 0.868

Asia WGS AF: 0.918 AC: 3191 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Oct 25, 2021	- -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

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	-0.89
CADD	Benign	1.9
DANN	Benign	0.34
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: rs3739495; hg19: chr9-134398534;