chr13-100515544-G-C
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM1BP4_StrongBP6BS2
The NM_000282.4(PCCA):āc.2017G>Cā(p.Val673Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00317 in 1,613,964 control chromosomes in the GnomAD database, including 9 homozygotes. 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V673I) has been classified as Uncertain significance.
Frequency
Consequence
NM_000282.4 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 |
---|---|---|---|---|---|---|---|
PCCA | NM_000282.4 | c.2017G>C | p.Val673Leu | missense_variant | 22/24 | ENST00000376285.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCCA | ENST00000376285.6 | c.2017G>C | p.Val673Leu | missense_variant | 22/24 | 1 | NM_000282.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00262 AC: 398AN: 152176Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.00247 AC: 621AN: 251292Hom.: 1 AF XY: 0.00254 AC XY: 345AN XY: 135812
GnomAD4 exome AF: 0.00323 AC: 4720AN: 1461670Hom.: 8 Cov.: 32 AF XY: 0.00321 AC XY: 2331AN XY: 727146
GnomAD4 genome AF: 0.00261 AC: 398AN: 152294Hom.: 1 Cov.: 33 AF XY: 0.00267 AC XY: 199AN XY: 74462
ClinVar
Submissions by phenotype
Propionic acidemia Uncertain:1Benign:2
Benign, no assertion criteria provided | clinical testing | Division of Genetic Medicine, Lausanne University Hospital | Jan 13, 2021 | The p.Val673Leu in PCCA has been found in homozygous state in three individuals without a phenotype of propionicacidemia. It has been previously identified as VUS but was never found in previous publications. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | PCCA: BP4 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 13, 2021 | - - |
PCCA-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 05, 2019 | 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