rs745318716
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The ENST00000640252.2(PIGN):āc.170A>Gā(p.Asp57Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000514 in 1,613,928 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 (ā ā ). Synonymous variant affecting the same amino acid position (i.e. D57D) has been classified as Likely benign.
Frequency
Consequence
ENST00000640252.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PIGN | NM_176787.5 | c.170A>G | p.Asp57Gly | missense_variant | 4/31 | ENST00000640252.2 | NP_789744.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PIGN | ENST00000640252.2 | c.170A>G | p.Asp57Gly | missense_variant | 4/31 | 1 | NM_176787.5 | ENSP00000492233 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152218Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000923 AC: 23AN: 249082Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135112
GnomAD4 exome AF: 0.0000534 AC: 78AN: 1461592Hom.: 0 Cov.: 30 AF XY: 0.0000798 AC XY: 58AN XY: 727056
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152336Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74494
ClinVar
Submissions by phenotype
Multiple congenital anomalies-hypotonia-seizures syndrome 1 Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Dec 05, 2017 | This variant was identified as homozygous - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 02, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 09, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 57 of the PIGN protein (p.Asp57Gly). This variant is present in population databases (rs745318716, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with PIGN-related conditions. ClinVar contains an entry for this variant (Variation ID: 580016). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 19, 2023 | The c.170A>G (p.D57G) alteration is located in exon 4 (coding exon 1) of the PIGN gene. This alteration results from a A to G substitution at nucleotide position 170, causing the aspartic acid (D) at amino acid position 57 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at