rs367627571
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_176787.5(PIGN):c.2596G>A(p.Val866Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000443 in 1,603,510 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_176787.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIGN | NM_176787.5 | c.2596G>A | p.Val866Ile | missense_variant | 29/31 | ENST00000640252.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGN | ENST00000640252.2 | c.2596G>A | p.Val866Ile | missense_variant | 29/31 | 1 | NM_176787.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000331 AC: 5AN: 151042Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000365 AC: 9AN: 246464Hom.: 0 AF XY: 0.0000449 AC XY: 6AN XY: 133682
GnomAD4 exome AF: 0.0000454 AC: 66AN: 1452468Hom.: 0 Cov.: 27 AF XY: 0.0000470 AC XY: 34AN XY: 722792
GnomAD4 genome ? AF: 0.0000331 AC: 5AN: 151042Hom.: 0 Cov.: 32 AF XY: 0.0000272 AC XY: 2AN XY: 73640
ClinVar
Submissions by phenotype
Multiple congenital anomalies-hypotonia-seizures syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces valine with isoleucine at codon 866 of the PIGN protein (p.Val866Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs367627571, ExAC 0.005%). This variant has not been reported in the literature in individuals affected with PIGN-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 15, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at