rs28941782
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_001077365.2(POMT1):c.226G>A(p.Gly76Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
POMT1
NM_001077365.2 missense
NM_001077365.2 missense
Scores
11
4
3
Clinical Significance
Conservation
PhyloP100: 9.36
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.974
PP5
?
Variant 9-131506217-G-A is Pathogenic according to our data. Variant chr9-131506217-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 3238.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-131506217-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POMT1 | NM_001077365.2 | c.226G>A | p.Gly76Arg | missense_variant | 3/20 | ENST00000402686.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POMT1 | ENST00000402686.8 | c.226G>A | p.Gly76Arg | missense_variant | 3/20 | 1 | NM_001077365.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461538Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727126
GnomAD4 exome
AF:
AC:
1
AN:
1461538
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
727126
Gnomad4 AFR exome
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Gnomad4 SAS exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2020 | - - |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2002 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;.;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;.;M;M;.;.
MutationTaster
Benign
A;A;A;A;A;A;A;A
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D;D
REVEL
Pathogenic
Sift
Benign
D;D;D;D;T;T
Sift4G
Benign
T;T;T;T;D;D
Polyphen
D;.;D;D;.;.
Vest4
MutPred
Gain of methylation at G76 (P = 7e-04);.;Gain of methylation at G76 (P = 7e-04);Gain of methylation at G76 (P = 7e-04);Gain of methylation at G76 (P = 7e-04);.;
MVP
MPC
0.97
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at