3-39383726-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PVS1_SupportingPM2
The NM_017875.4(SLC25A38):āc.2T>Cā(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,613,944 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_017875.4 start_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC25A38 | NM_017875.4 | c.2T>C | p.Met1? | start_lost | Exon 1 of 7 | ENST00000650617.1 | NP_060345.2 | |
SLC25A38 | NM_001354798.2 | c.2T>C | p.Met1? | start_lost | Exon 1 of 6 | NP_001341727.1 | ||
LOC105377644 | XR_007096252.1 | n.85+515A>G | intron_variant | Intron 1 of 2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152166Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 250952Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135778
GnomAD4 exome AF: 0.0000417 AC: 61AN: 1461778Hom.: 0 Cov.: 31 AF XY: 0.0000440 AC XY: 32AN XY: 727200
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152166Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74324
ClinVar
Submissions by phenotype
SLC25A38-related disorder Uncertain:1
This variant is predicted to disrupt the initiator codon and thus potentially may interfere with protein expression. It was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018) and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene and cDNA change, and amino acid change. No publications were found based on this search. Due to the potential impact on protein expression and the lack of clarifying evidence, this variant is classified as a variant of uncertain significance but suspicious for pathogenicity for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at