rs372739944
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BP6
The NM_000282.4(PCCA):c.819+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000336 in 1,012,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
PCCA
NM_000282.4 intron
NM_000282.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.658
Genes affected
PCCA (HGNC:8653): (propionyl-CoA carboxylase subunit alpha) The protein encoded by this gene is the alpha subunit of the heterodimeric mitochondrial enzyme Propionyl-CoA carboxylase. PCCA encodes the biotin-binding region of this enzyme. Mutations in either PCCA or PCCB (encoding the beta subunit) lead to an enzyme deficiency resulting in propionic acidemia. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
BP6
?
Variant 13-100262840-A-G is Benign according to our data. Variant chr13-100262840-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 568750.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCCA | NM_000282.4 | c.819+9A>G | intron_variant | ENST00000376285.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCCA | ENST00000376285.6 | c.819+9A>G | intron_variant | 1 | NM_000282.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152154Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000244 AC: 6AN: 245948Hom.: 0 AF XY: 0.00000750 AC XY: 1AN XY: 133402
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GnomAD4 exome AF: 0.0000337 AC: 29AN: 860060Hom.: 0 Cov.: 12 AF XY: 0.0000442 AC XY: 20AN XY: 452318
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74326
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Propionic acidemia Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | in vitro;research | Laboratory of Inherited Metabolic Diseases, Research centre for medical genetics | Feb 17, 2021 | PM2, BS3 - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -5
Find out detailed SpliceAI scores and Pangolin per-transcript scores at