chr2-171785338-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_003705.5(SLC25A12):c.1973C>T(p.Pro658Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,854 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. P658P) has been classified as Likely benign.
Frequency
Consequence
NM_003705.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC25A12 | NM_003705.5 | c.1973C>T | p.Pro658Leu | missense_variant | 18/18 | ENST00000422440.7 | |
SLC25A12 | XM_047446142.1 | c.1700C>T | p.Pro567Leu | missense_variant | 16/16 | ||
SLC25A12 | NR_047549.2 | n.1887C>T | non_coding_transcript_exon_variant | 17/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC25A12 | ENST00000422440.7 | c.1973C>T | p.Pro658Leu | missense_variant | 18/18 | 1 | NM_003705.5 | P1 | |
SLC25A12 | ENST00000472070.1 | n.1383C>T | non_coding_transcript_exon_variant | 3/3 | 2 | ||||
SLC25A12 | ENST00000263812.8 | c.*1593C>T | 3_prime_UTR_variant, NMD_transcript_variant | 17/17 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251484Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135916
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461854Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727228
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2023 | 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. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 658 of the SLC25A12 protein (p.Pro658Leu). This variant is present in population databases (rs754742634, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SLC25A12-related conditions. ClinVar contains an entry for this variant (Variation ID: 1051699). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at