rs778907895
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_032806.6(POMGNT2):c.332G>A(p.Arg111His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,614,046 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
POMGNT2
NM_032806.6 missense
NM_032806.6 missense
Scores
9
2
7
Clinical Significance
Conservation
PhyloP100: 7.91
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.918
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POMGNT2 | NM_032806.6 | c.332G>A | p.Arg111His | missense_variant | 2/2 | ENST00000344697.3 | |
POMGNT2 | XM_005265515.4 | c.332G>A | p.Arg111His | missense_variant | 3/3 | ||
POMGNT2 | XM_011534163.3 | c.332G>A | p.Arg111His | missense_variant | 3/3 | ||
POMGNT2 | XM_017007353.2 | c.332G>A | p.Arg111His | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POMGNT2 | ENST00000344697.3 | c.332G>A | p.Arg111His | missense_variant | 2/2 | 1 | NM_032806.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152164Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251436Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135902
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461882Hom.: 0 Cov.: 37 AF XY: 0.0000110 AC XY: 8AN XY: 727242
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152164Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74346
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 03, 2022 | This variant is present in population databases (rs778907895, gnomAD 0.006%). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 540495). This variant has not been reported in the literature in individuals affected with POMGNT2-related conditions. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 111 of the POMGNT2 protein (p.Arg111His). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Pathogenic
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MutPred
Loss of methylation at R111 (P = 0.1);Loss of methylation at R111 (P = 0.1);
MVP
MPC
1.0
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at