chr1-231241443-T-C
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_014236.4(GNPAT):āc.65T>Cā(p.Val22Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,612,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V22V) has been classified as Likely benign.
Frequency
Consequence
NM_014236.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNPAT | NM_014236.4 | c.65T>C | p.Val22Ala | missense_variant | 1/16 | ENST00000366647.9 | |
GNPAT | NM_001316350.2 | c.65T>C | p.Val22Ala | missense_variant | 1/15 | ||
GNPAT | XM_005273313.5 | c.65T>C | p.Val22Ala | missense_variant | 1/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNPAT | ENST00000366647.9 | c.65T>C | p.Val22Ala | missense_variant | 1/16 | 1 | NM_014236.4 | P1 | |
GNPAT | ENST00000416000.1 | c.65T>C | p.Val22Ala | missense_variant | 1/13 | 5 | |||
GNPAT | ENST00000436239.5 | c.65T>C | p.Val22Ala | missense_variant | 1/6 | 3 | |||
GNPAT | ENST00000644483.1 | c.65T>C | p.Val22Ala | missense_variant, NMD_transcript_variant | 1/17 |
Frequencies
GnomAD3 genomes AF: 0.000933 AC: 142AN: 152188Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000233 AC: 58AN: 248992Hom.: 0 AF XY: 0.000171 AC XY: 23AN XY: 134794
GnomAD4 exome AF: 0.0000959 AC: 140AN: 1460222Hom.: 0 Cov.: 31 AF XY: 0.0000798 AC XY: 58AN XY: 726624
GnomAD4 genome AF: 0.000932 AC: 142AN: 152306Hom.: 0 Cov.: 33 AF XY: 0.000806 AC XY: 60AN XY: 74474
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 21, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Rhizomelic chondrodysplasia punctata type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 28, 2019 | The GNPAT c.65T>C; p.Val22Ala variant (rs143388851), to our knowledge, is not reported in the medical literature or gene-specific databases. This variant is found in the African population with an overall allele frequency of 0.35% (87/24968 alleles) in the Genome Aggregation Database. The valine at codon 22 is moderately conserved, and computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. Given the lack of clinical and functional data, the significance of the p.Val22Ala variant is uncertain at this time. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at