9-131510049-A-G

Variant names:

Variant summary

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

The ENST00000372228.9(POMT1):c.752A>G(p.Gln251Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.94 in 1,614,106 control chromosomes in the GnomAD database, including 714,950 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.89 ( 60620 hom., cov: 33)

Exomes 𝑓: 0.95 ( 654330 hom. )

Consequence

POMT1
ENST00000372228.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.989

Publications

47 publications found

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 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 (MetaRNN=2.4782473E-6).

BP6

Variant 9-131510049-A-G is Benign according to our data. Variant chr9-131510049-A-G is described in ClinVar as Benign. ClinVar VariationId is 227021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000372228.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
POMT1	NM_001077365.2	MANE Select	c.699+53A>G		intron	N/A	NP_001070833.1
POMT1	NM_001353193.2		c.752A>G	p.Gln251Arg	missense	Exon 8 of 20	NP_001340122.2
POMT1	NM_007171.4		c.752A>G	p.Gln251Arg	missense	Exon 8 of 20	NP_009102.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
POMT1	ENST00000372228.9	TSL:1	c.752A>G	p.Gln251Arg	missense	Exon 8 of 20	ENSP00000361302.3
POMT1	ENST00000423007.6	TSL:1	c.743A>G	p.Gln248Arg	missense	Exon 7 of 19	ENSP00000404119.2
POMT1	ENST00000402686.8	TSL:1 MANE Select	c.699+53A>G		intron	N/A	ENSP00000385797.4

Frequencies

GnomAD3 genomes

AF:

0.887

AC:

134972

AN:

152110

Hom.:

60591

Cov.:

show subpopulations

Gnomad AFR

AF:

0.746

Gnomad AMI

AF:

0.899

Gnomad AMR

AF:

0.861

Gnomad ASJ

AF:

0.942

Gnomad EAS

AF:

0.918

Gnomad SAS

AF:

0.970

Gnomad FIN

AF:

0.978

Gnomad MID

AF:

0.915

Gnomad NFE

AF:

0.954

Gnomad OTH

AF:

0.895

GnomAD2 exomes

AF:

0.924

AC:

231971

AN:

251126

AF XY:

0.932

show subpopulations

Gnomad AFR exome

AF:

0.734

Gnomad AMR exome

AF:

0.841

Gnomad ASJ exome

AF:

0.943

Gnomad EAS exome

AF:

0.914

Gnomad FIN exome

AF:

0.977

Gnomad NFE exome

AF:

0.953

Gnomad OTH exome

AF:

0.931

GnomAD4 exome

AF:

0.945

AC:

1381729

AN:

1461878

Hom.:

654330

Cov.:

AF XY:

0.947

AC XY:

688666

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.732

AC:

24507

AN:

33478

American (AMR)

AF:

0.842

AC:

37664

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.942

AC:

24632

AN:

26136

East Asian (EAS)

AF:

0.916

AC:

36378

AN:

39700

South Asian (SAS)

AF:

0.971

AC:

83716

AN:

86254

European-Finnish (FIN)

AF:

0.976

AC:

52149

AN:

53418

Middle Eastern (MID)

AF:

0.936

AC:

5397

AN:

5768

European-Non Finnish (NFE)

AF:

0.954

AC:

1061255

AN:

1112006

Other (OTH)

AF:

0.928

AC:

56031

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

5286

10571

15857

21142

26428

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21602

43204

64806

86408

108010

<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:

0.887

AC:

135043

AN:

152228

Hom.:

60620

Cov.:

AF XY:

0.889

AC XY:

66184

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.745

AC:

30913

AN:

41494

American (AMR)

AF:

0.861

AC:

13175

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.942

AC:

3269

AN:

3472

East Asian (EAS)

AF:

0.918

AC:

4752

AN:

5178

South Asian (SAS)

AF:

0.971

AC:

4683

AN:

4824

European-Finnish (FIN)

AF:

0.978

AC:

10382

AN:

10620

Middle Eastern (MID)

AF:

0.915

AC:

269

AN:

294

European-Non Finnish (NFE)

AF:

0.954

AC:

64889

AN:

68024

Other (OTH)

AF:

0.895

AC:

1893

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

712

1425

2137

2850

3562

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<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:

0.931

Hom.:

328153

Bravo

AF:

0.869

TwinsUK

AF:

0.960

AC:

3559

ALSPAC

AF:

0.955

AC:

3682

ESP6500AA

AF:

0.738

AC:

3253

ESP6500EA

AF:

0.952

AC:

8183

ExAC

AF:

0.923

AC:

112055

Asia WGS

AF:

0.910

AC:

3164

AN:

3478

EpiCase

AF:

0.949

EpiControl

AF:

0.947

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Dec 11, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This is a RefSeq error. The reference base (c.752A) is the minor allele. This al lele (A) has been identified in 5% (417/8600) of European American chromosomes a nd 26% (1153/4406) of African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs2296949).

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

CADD

Benign

1.8

(source)

DANN

Benign

0.16

DEOGEN2

Benign

0.17

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00028

LIST_S2

Benign

0.13

MetaRNN

Benign

0.0000025

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

PhyloP100

-0.99

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.080

REVEL

Benign

0.20

Sift

Benign

0.61

Sift4G

Benign

0.50

Polyphen

0.0

Vest4

0.0080

MPC

0.26

ClinPred

0.00016

GERP RS

1.3

PromoterAI

0.015

Neutral

(source)

Varity_R

0.014

gMVP

0.052

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over