7-96121309-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_014251.3(SLC25A13):āc.1910T>Cā(p.Val637Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00026 in 1,614,082 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_014251.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC25A13 | ENST00000265631.10 | c.1910T>C | p.Val637Ala | missense_variant | Exon 18 of 18 | 1 | NM_014251.3 | ENSP00000265631.6 | ||
SLC25A13 | ENST00000416240.6 | c.1913T>C | p.Val638Ala | missense_variant | Exon 18 of 18 | 1 | ENSP00000400101.2 | |||
SLC25A13 | ENST00000494085.1 | n.413T>C | non_coding_transcript_exon_variant | Exon 2 of 2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000664 AC: 101AN: 152092Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000259 AC: 65AN: 251420Hom.: 0 AF XY: 0.000206 AC XY: 28AN XY: 135876
GnomAD4 exome AF: 0.000218 AC: 318AN: 1461872Hom.: 0 Cov.: 31 AF XY: 0.000215 AC XY: 156AN XY: 727236
GnomAD4 genome AF: 0.000664 AC: 101AN: 152210Hom.: 1 Cov.: 32 AF XY: 0.000699 AC XY: 52AN XY: 74434
ClinVar
Submissions by phenotype
not provided Uncertain:2
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In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Citrullinemia type II Uncertain:1
This variant was observed in the ICSL laboratory 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, this variant 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, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Late-onset citrullinemia Uncertain:1
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Citrullinemia type I Uncertain:1
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Neonatal intrahepatic cholestasis due to citrin deficiency;C1863844:Citrullinemia type II Uncertain:1
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Citrin deficiency Benign:1
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SLC25A13-related disorder Benign:1
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