7-96131829-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_014251.3(SLC25A13):c.1505C>T(p.Pro502Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000799 in 1,613,930 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC25A13 | ENST00000265631.10 | c.1505C>T | p.Pro502Leu | missense_variant | Exon 15 of 18 | 1 | NM_014251.3 | ENSP00000265631.6 | ||
SLC25A13 | ENST00000416240.6 | c.1508C>T | p.Pro503Leu | missense_variant | Exon 15 of 18 | 1 | ENSP00000400101.2 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152094Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000179 AC: 45AN: 250864Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135652
GnomAD4 exome AF: 0.0000773 AC: 113AN: 1461836Hom.: 1 Cov.: 31 AF XY: 0.0000853 AC XY: 62AN XY: 727208
GnomAD4 genome AF: 0.000105 AC: 16AN: 152094Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74284
ClinVar
Submissions by phenotype
Neonatal intrahepatic cholestasis due to citrin deficiency Pathogenic:1
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Citrullinemia, type II, adult-onset Pathogenic:1
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Citrullinemia type II Uncertain:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
not provided Uncertain:1
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SLC25A13-related disorder Uncertain:1
The SLC25A13 c.1505C>T variant is predicted to result in the amino acid substitution p.Pro502Leu. This variant has been reported in a patient with questionable diagnosis of neonatal intrahepatic cholestasis and was shown in functional studies to be fully functional (Wongkittichote et al. 2013. PubMed ID: 21507300; Wen et al. 2011. PubMed ID: 23053473). This variant is reported in 0.17% to 0.20% of alleles, including one homozygous, in individuals of Ashkenazi Jewish descent in gnomAD datasets. Although we suspect that this variant may be benign, the clinical significance of this variant is classified as uncertain at this time due to insufficient functional and genetic evidence. -
Citrin deficiency Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at