7-96121876-AC-A
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_014251.3(SLC25A13):c.1712del(p.Arg571LeufsTer25) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
SLC25A13
NM_014251.3 frameshift
NM_014251.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.326
Genes affected
SLC25A13 (HGNC:10983): (solute carrier family 25 member 13) This gene is a member of the mitochondrial carrier family. The encoded protein contains four EF-hand Ca(2+) binding motifs in the N-terminal domain, and localizes to mitochondria. The protein catalyzes the exchange of aspartate for glutamate and a proton across the inner mitochondrial membrane, and is stimulated by calcium on the external side of the inner mitochondrial membrane. Mutations in this gene result in citrullinemia, type II. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 7-96121876-AC-A is Pathogenic according to our data. Variant chr7-96121876-AC-A is described in ClinVar as [Pathogenic]. Clinvar id is 469032.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC25A13 | NM_014251.3 | c.1712del | p.Arg571LeufsTer25 | frameshift_variant | 16/18 | ENST00000265631.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC25A13 | ENST00000265631.10 | c.1712del | p.Arg571LeufsTer25 | frameshift_variant | 16/18 | 1 | NM_014251.3 | A1 | |
SLC25A13 | ENST00000416240.6 | c.1715del | p.Arg572LeufsTer25 | frameshift_variant | 16/18 | 1 | P5 | ||
SLC25A13 | ENST00000494085.1 | n.122del | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727248
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GnomAD4 genome Cov.: 33
GnomAD4 genome
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33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Citrin deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2016 | This sequence change deletes 1 nucleotide from exon 16 of the SLC25A13 mRNA (c.1712delG), causing a frameshift at codon 571. This creates a premature translational stop signal (p.Arg571Leufs*25) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in SLC25A13 are known to be pathogenic (PMID: 14680984). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at