17-81715568-A-T
Position:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_012140.5(SLC25A10):c.304A>T(p.Lys102*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 34)
Consequence
SLC25A10
NM_012140.5 stop_gained
NM_012140.5 stop_gained
Scores
3
3
1
Clinical Significance
Conservation
PhyloP100: 8.25
Genes affected
SLC25A10 (HGNC:10980): (solute carrier family 25 member 10) This gene encodes a member of a family of proteins that translocate small metabolites across the mitochondrial membrane. The encoded protein exchanges dicarboxylates, such as malate and succinate, for phosphate, sulfate, and other small molecules, thereby providing substrates for metabolic processes including the Krebs cycle and fatty acid synthesis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 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 17-81715568-A-T is Pathogenic according to our data. Variant chr17-81715568-A-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 446175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-81715568-A-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC25A10 | NM_012140.5 | c.304A>T | p.Lys102* | stop_gained | 3/11 | ENST00000350690.10 | NP_036272.2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 genomes
Cov.:
34
GnomAD4 exome Cov.: 36
GnomAD4 exome
Cov.:
36
GnomAD4 genome Cov.: 34
GnomAD4 genome
Cov.:
34
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Mitochondrial DNA depletion syndrome 19 Pathogenic:2
Likely pathogenic, criteria provided, single submitter | curation | SIB Swiss Institute of Bioinformatics | Apr 01, 2021 | This variant is interpreted as a likely pathogenic for Mitochondrial DNA depletion syndrome 19, autosomal recessive. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); Predicted nullvariant in a gene where LOF is a known mechanism of disease (PVS1 downgraded to moderate); Well-established functional studies show a deleterious effect (PS3 downgraded to moderate). - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 10, 2020 | - - |
Mitochondrial complex I deficiency Pathogenic:1
Likely pathogenic, criteria provided, single submitter | in vitro;research | Computational Biology Unit, University of Bari | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at