13-100111820-ATG-A
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_000282.4(PCCA):c.184-17_184-16delGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,563,578 control chromosomes in the GnomAD database, including 9,092 homozygotes. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000282.4 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.118 AC: 17897AN: 151908Hom.: 1212 Cov.: 30
GnomAD3 exomes AF: 0.0929 AC: 22682AN: 244140Hom.: 1230 AF XY: 0.0949 AC XY: 12515AN XY: 131902
GnomAD4 exome AF: 0.0995 AC: 140483AN: 1411550Hom.: 7878 AF XY: 0.0997 AC XY: 70282AN XY: 704592
GnomAD4 genome AF: 0.118 AC: 17933AN: 152028Hom.: 1214 Cov.: 30 AF XY: 0.115 AC XY: 8560AN XY: 74326
ClinVar
Submissions by phenotype
not specified Benign:8
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Variant summary: PCCA c.184-17_184-16delGT alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.093 in 244140 control chromosomes in the gnomAD database, including 1230 homozygotes. The observed variant frequency is approximately 27-folds over the estimated maximal expected allele frequency for a pathogenic variant in PCCA causing Propionic Acidemia phenotype (0.0034), strongly suggesting that the variant is benign. Two ClinVar submissions (evaluation after 2014) cites the variant as benign. Based on the evidence outlined above, the variant was classified as benign. -
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The variant is found in UCD-MET panel(s). -
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Propionic acidemia Benign:4
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at