rs59515295

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 1.08

Publications

5 publications found

Variant links:

COSMIC-nc: COSV61225183

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

POMT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMT1	NM_001077365.2 link	c.1082+16G>A		intron_variant	Intron 11 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.1082+16G>A		intron_variant	Intron 11 of 19	1	NM_001077365.2	ENSP00000385797.4		Q9Y6A1-2

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

21050

AN:

152006

Hom.:

1610

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.129

AC XY:

93525

AN XY:

726334

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

10129

20257

30386

40514

50643

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5440

10880

16320

21760

27200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.138

AC:

21062

AN:

152124

Hom.:

1611

Cov.:

AF XY:

0.139

AC XY:

10359

AN XY:

74396

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.146

AC:

9905

AN:

67964

Other (OTH)

AF:

0.128

AC:

271

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

895

1790

2684

3579

4474

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

220

440

660

880

1100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

LINK: link

Submissions by phenotype

not specified

Benign:6

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. -

Jul 24, 2012

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

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

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic 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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.2

(source)

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over