chr12-94971615-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_018838.5(NDUFA12):c.263G>A(p.Arg88His) variant causes a missense change. The variant allele was found at a frequency of 0.0000514 in 1,613,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R88C) has been classified as Uncertain significance.
Frequency
Consequence
NM_018838.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NDUFA12 | NM_018838.5 | c.263G>A | p.Arg88His | missense_variant | 4/4 | ENST00000327772.7 | |
NDUFA12 | NM_001258338.2 | c.175G>A | p.Val59Ile | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NDUFA12 | ENST00000327772.7 | c.263G>A | p.Arg88His | missense_variant | 4/4 | 1 | NM_018838.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000210 AC: 32AN: 152024Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000756 AC: 19AN: 251264Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135818
GnomAD4 exome AF: 0.0000349 AC: 51AN: 1461848Hom.: 0 Cov.: 31 AF XY: 0.0000413 AC XY: 30AN XY: 727228
GnomAD4 genome AF: 0.000210 AC: 32AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74374
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 29, 2022 | The c.263G>A (p.R88H) alteration is located in exon 4 (coding exon 4) of the NDUFA12 gene. This alteration results from a G to A substitution at nucleotide position 263, causing the arginine (R) at amino acid position 88 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 88 of the NDUFA12 protein (p.Arg88His). This variant is present in population databases (rs371084211, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with NDUFA12-related conditions. ClinVar contains an entry for this variant (Variation ID: 1509281). 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 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