rs538760468
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003850.3(SUCLA2):c.68C>T(p.Thr23Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000311 in 1,609,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T23R) has been classified as Uncertain significance.
Frequency
Consequence
NM_003850.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SUCLA2 | NM_003850.3 | c.68C>T | p.Thr23Met | missense_variant | 1/11 | ENST00000646932.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SUCLA2 | ENST00000646932.1 | c.68C>T | p.Thr23Met | missense_variant | 1/11 | NM_003850.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152196Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000168 AC: 4AN: 238296Hom.: 0 AF XY: 0.0000154 AC XY: 2AN XY: 129974
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1457306Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 724692
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152196Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74354
ClinVar
Submissions by phenotype
Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 12, 2022 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 23 of the SUCLA2 protein (p.Thr23Met). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SUCLA2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at