rs201902280
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_014252.4(SLC25A15):c.380C>T(p.Thr127Met) variant causes a missense change. The variant allele was found at a frequency of 0.000155 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T127T) has been classified as Likely benign.
Frequency
Consequence
NM_014252.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC25A15 | NM_014252.4 | c.380C>T | p.Thr127Met | missense_variant | 4/7 | ENST00000338625.9 | |
TPTE2P5 | NR_038259.1 | n.452-4459G>A | intron_variant, non_coding_transcript_variant | ||||
TPTE2P5 | NR_038258.1 | n.623-4459G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC25A15 | ENST00000338625.9 | c.380C>T | p.Thr127Met | missense_variant | 4/7 | 1 | NM_014252.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152168Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251466Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135906
GnomAD4 exome AF: 0.000160 AC: 234AN: 1461874Hom.: 0 Cov.: 32 AF XY: 0.000150 AC XY: 109AN XY: 727236
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74332
ClinVar
Submissions by phenotype
Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome Uncertain:4
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | May 02, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 12, 2022 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 127 of the SLC25A15 protein (p.Thr127Met). This variant is present in population databases (rs201902280, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SLC25A15-related conditions. ClinVar contains an entry for this variant (Variation ID: 547845). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SLC25A15 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 16, 2021 | The c.380C>T (p.T127M) alteration is located in exon 4 (coding exon 3) of the SLC25A15 gene. This alteration results from a C to T substitution at nucleotide position 380, causing the threonine (T) at amino acid position 127 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at