9-131512152-G-A

Variant names:

• chr9-131512152-G-A
• rs59515295
• NM_001077365.2:c.1082+16G>A

Variant summary

Our verdict is Benign. The variant received -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:11
• Conservation: PhyloP100: 1.08
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

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

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Laboratory for Molecular Medicine, Genomics England PanelApp
• myopathy caused by variation in POMT1

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• autosomal recessive limb-girdle muscular dystrophy type 2K

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• congenital muscular dystrophy with cerebellar involvement

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• congenital muscular dystrophy with intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• congenital muscular dystrophy without intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• muscle-eye-brain disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• muscular dystrophy-dystroglycanopathy, type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 95451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077365.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMT1	NM_001077365.2	MANE Select	c.1082+16G>A		intron	N/A	NP_001070833.1
	POMT1	NM_001353193.2		c.1148+16G>A		intron	N/A	NP_001340122.2
	POMT1	NM_007171.4		c.1148+16G>A		intron	N/A	NP_009102.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMT1	ENST00000402686.8	TSL:1 MANE Select	c.1082+16G>A		intron	N/A	ENSP00000385797.4
	POMT1	ENST00000372228.9	TSL:1	c.1148+16G>A		intron	N/A	ENSP00000361302.3
	POMT1	ENST00000423007.6	TSL:1	c.1139+16G>A		intron	N/A	ENSP00000404119.2

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

GnomAD2 exomes AF: 0.116 AC: 28784 AN: 248402 AF XY: 0.113

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 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

African (AFR) AF: 0.149 AC: 5002 AN: 33468

American (AMR) AF: 0.0696 AC: 3100 AN: 44554

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 3401 AN: 26086

East Asian (EAS) AF: 0.000328 AC: 13 AN: 39676

South Asian (SAS) AF: 0.0537 AC: 4618 AN: 86006

European-Finnish (FIN) AF: 0.201 AC: 10714 AN: 53258

Middle Eastern (MID) AF: 0.0534 AC: 307 AN: 5744

European-Non Finnish (NFE) AF: 0.141 AC: 157085 AN: 1111234

Other (OTH) AF: 0.122 AC: 7350 AN: 60342

GnomAD4 genome AF: 0.138 AC: 21062 AN: 152124 Hom.: 1611 Cov.: 31 AF XY: 0.139 AC XY: 10359 AN XY: 74396

African (AFR) AF: 0.154 AC: 6401 AN: 41492

American (AMR) AF: 0.108 AC: 1657 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 431 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.0488 AC: 235 AN: 4812

European-Finnish (FIN) AF: 0.192 AC: 2033 AN: 10590

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9905 AN: 67964

Other (OTH) AF: 0.128 AC: 271 AN: 2112

Alfa AF: 0.145 Hom.: 722

Bravo AF: 0.130

Asia WGS AF: 0.0330 AC: 117 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

Jul 24, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Dec 19, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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.

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

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

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.2
DANN	Benign	0.70
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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