rs142192097
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_017837.4(PIGV):āc.349A>Gā(p.Ile117Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,614,180 control chromosomes in the GnomAD database, including 4 homozygotes. 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_017837.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIGV | NM_017837.4 | c.349A>G | p.Ile117Val | missense_variant | 3/4 | ENST00000674202.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGV | ENST00000674202.1 | c.349A>G | p.Ile117Val | missense_variant | 3/4 | NM_017837.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000940 AC: 143AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00139 AC: 349AN: 251466Hom.: 0 AF XY: 0.00141 AC XY: 191AN XY: 135918
GnomAD4 exome AF: 0.00170 AC: 2482AN: 1461892Hom.: 4 Cov.: 34 AF XY: 0.00166 AC XY: 1209AN XY: 727248
GnomAD4 genome ? AF: 0.000939 AC: 143AN: 152288Hom.: 0 Cov.: 32 AF XY: 0.000792 AC XY: 59AN XY: 74462
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 19, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 28, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Hyperphosphatasia with intellectual disability syndrome 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Jun 18, 2020 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: See c.348G>A. These two variants result in c.348_349delinsAG. (p.Ile117Val). Not reported. MAF 0.25%. Gene is associated with AR hyperphosphatasia with mental retardation syndrome. Severe end of the spectrum presents with multiple congenital anomalies, including Hirschsprung disease, vesicoureteral, and renal anomalies as well as anorectal malformations. Developmental delays, particular facial anomalies, brachytelephalangy, and hyperphosphatasia are consistently found. VUS3, but the gene may explain the patient's phenotype, so may report in IBA report. - OB 10/22/15: Decided to not include in the report, since it is a VUS3 in a recessive gene not well-associated with the patient's pehnotype, and the variant is heterozygous. - |
PIGV-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 22, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at