9-131506100-GT-GTT

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

1 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 -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 Benign/Likely_benign. ClinVar VariationId 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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
POMT1	NM_001077365.2	MANE Select	c.123-5dupT	splice_region intron	N/A	NP_001070833.1
POMT1	NM_001353193.2		c.123-5dupT	splice_region intron	N/A	NP_001340122.2
POMT1	NM_007171.4		c.123-5dupT	splice_region intron	N/A	NP_009102.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
POMT1	ENST00000402686.8	TSL:1 MANE Select	c.123-5dupT	splice_region intron	N/A	ENSP00000385797.4
POMT1	ENST00000372228.9	TSL:1	c.123-5dupT	splice_region intron	N/A	ENSP00000361302.3
POMT1	ENST00000423007.6	TSL:1	c.123-5dupT	splice_region intron	N/A	ENSP00000404119.2

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

GnomAD2 exomes

AF:

0.115

AC:

27334

AN:

238246

AF XY:

0.114

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 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

African (AFR)

AF:

0.0566

AC:

1844

AN:

32608

American (AMR)

AF:

0.0675

AC:

2966

AN:

43942

Ashkenazi Jewish (ASJ)

AF:

0.130

AC:

3306

AN:

25462

East Asian (EAS)

AF:

0.00643

AC:

244

AN:

37950

South Asian (SAS)

AF:

0.0565

AC:

4797

AN:

84922

European-Finnish (FIN)

AF:

0.216

AC:

11160

AN:

51696

Middle Eastern (MID)

AF:

0.0447

AC:

252

AN:

5632

European-Non Finnish (NFE)

AF:

0.145

AC:

156512

AN:

1082976

Other (OTH)

AF:

0.119

AC:

6968

AN:

58686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

8862

17723

26585

35446

44308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5480

10960

16440

21920

27400

<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:

0.117

AC:

17709

AN:

151334

Hom.:

1260

Cov.:

AF XY:

0.120

AC XY:

8865

AN XY:

73900

show subpopulations

African (AFR)

AF:

0.0623

AC:

2568

AN:

41228

American (AMR)

AF:

0.101

AC:

1539

AN:

15204

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

434

AN:

3456

East Asian (EAS)

AF:

0.00851

AC:

AN:

5170

South Asian (SAS)

AF:

0.0516

AC:

247

AN:

4784

European-Finnish (FIN)

AF:

0.216

AC:

2249

AN:

10404

Middle Eastern (MID)

AF:

0.0345

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.151

AC:

10257

AN:

67792

Other (OTH)

AF:

0.112

AC:

234

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

770

1541

2311

3082

3852

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<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:

0.0823

Hom.:

139

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

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%

Dec 17, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

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

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 v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.22

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

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