3-48898707-G-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000387.6(SLC25A20):c.88C>G(p.Pro30Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,606,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000387.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC25A20 | ENST00000319017.5 | c.88C>G | p.Pro30Ala | missense_variant | Exon 1 of 9 | 1 | NM_000387.6 | ENSP00000326305.4 | ||
SLC25A20 | ENST00000430379.5 | c.88C>G | p.Pro30Ala | missense_variant | Exon 1 of 7 | 3 | ENSP00000388986.1 | |||
SLC25A20 | ENST00000440964.1 | n.88C>G | non_coding_transcript_exon_variant | Exon 1 of 10 | 2 | ENSP00000388563.1 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152236Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000128 AC: 3AN: 234936Hom.: 0 AF XY: 0.00000782 AC XY: 1AN XY: 127940
GnomAD4 exome AF: 0.00000688 AC: 10AN: 1454022Hom.: 0 Cov.: 31 AF XY: 0.00000553 AC XY: 4AN XY: 722856
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74376
ClinVar
Submissions by phenotype
Carnitine acylcarnitine translocase deficiency Uncertain:1
This sequence change replaces proline with alanine at codon 30 of the SLC25A20 protein (p.Pro30Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. This variant is present in population databases (rs780569251, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with SLC25A20-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
See cases Uncertain:1
ACMG classification criteria: PP3, BP1 -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at