rs3739494

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001077365.2(POMT1):​c.1047T>C​(p.Asp349Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.94 in 1,613,944 control chromosomes in the GnomAD database, including 714,925 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.89 ( 60599 hom., cov: 31)
Exomes 𝑓: 0.95 ( 654326 hom. )

Consequence

POMT1
NM_001077365.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.54
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
Variant 9-131512101-T-C is Benign according to our data. Variant chr9-131512101-T-C is described in ClinVar as [Benign]. Clinvar id is 167520.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-131512101-T-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-1.54 with no splicing effect.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
POMT1NM_001077365.2 linkc.1047T>C p.Asp349Asp synonymous_variant Exon 11 of 20 ENST00000402686.8 NP_001070833.1 Q9Y6A1-2A0A140VKE0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
POMT1ENST00000402686.8 linkc.1047T>C p.Asp349Asp synonymous_variant Exon 11 of 20 1 NM_001077365.2 ENSP00000385797.4 Q9Y6A1-2

Frequencies

GnomAD3 genomes
AF:
0.888
AC:
134901
AN:
151990
Hom.:
60568
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.746
Gnomad AMI
AF:
0.899
Gnomad AMR
AF:
0.861
Gnomad ASJ
AF:
0.941
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:
232202
AN:
251354
AF XY:
0.932
show subpopulations
Gnomad AFR exome
AF:
0.735
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:
1381715
AN:
1461836
Hom.:
654326
Cov.:
94
AF XY:
0.947
AC XY:
688653
AN XY:
727208
show subpopulations
Gnomad4 AFR exome
AF:
0.732
AC:
24520
AN:
33480
Gnomad4 AMR exome
AF:
0.842
AC:
37654
AN:
44706
Gnomad4 ASJ exome
AF:
0.942
AC:
24632
AN:
26136
Gnomad4 EAS exome
AF:
0.916
AC:
36374
AN:
39698
Gnomad4 SAS exome
AF:
0.971
AC:
83704
AN:
86244
Gnomad4 FIN exome
AF:
0.976
AC:
52144
AN:
53414
Gnomad4 NFE exome
AF:
0.954
AC:
1061248
AN:
1111994
Gnomad4 Remaining exome
AF:
0.928
AC:
56040
AN:
60396
Heterozygous variant carriers
0
4992
9983
14975
19966
24958
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
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:
134974
AN:
152108
Hom.:
60599
Cov.:
31
AF XY:
0.889
AC XY:
66130
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.746
AC:
0.745573
AN:
0.745573
Gnomad4 AMR
AF:
0.861
AC:
0.861424
AN:
0.861424
Gnomad4 ASJ
AF:
0.941
AC:
0.941499
AN:
0.941499
Gnomad4 EAS
AF:
0.918
AC:
0.918122
AN:
0.918122
Gnomad4 SAS
AF:
0.971
AC:
0.970552
AN:
0.970552
Gnomad4 FIN
AF:
0.978
AC:
0.977847
AN:
0.977847
Gnomad4 NFE
AF:
0.954
AC:
0.953928
AN:
0.953928
Gnomad4 OTH
AF:
0.897
AC:
0.89678
AN:
0.89678
Heterozygous variant carriers
0
701
1402
2103
2804
3505
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
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:
0.930
Hom.:
128788
Bravo
AF:
0.869
Asia WGS
AF:
0.917
AC:
3189
AN:
3478
EpiCase
AF:
0.949
EpiControl
AF:
0.947

ClinVar

Significance: Benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:5
Nov 26, 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.1113T) is the minor allele. This a llele (T) has been identified in 5% (411/8600) of European American chromosomes and 26% (1143/4406) of African American chromosomes by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS/; dbSNP rs3739494) and thus meets cr iteria to be classified as benign. -

Apr 23, 2013
Eurofins Ntd Llc (ga)
Significance:Benign
Review Status:criteria provided, single submitter
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

- -

-
Clinical Genetics, Academic Medical Center
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

-
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
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
-0.59
CADD
Benign
0.49
DANN
Benign
0.67
Mutation Taster
=94/6
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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3739494; hg19: chr9-134387488; COSMIC: COSV108169146; COSMIC: COSV108169146; API