rs151344523
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong
The NM_006796.3(AFG3L2):c.2105G>A(p.Arg702Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,910 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 Likely pathogenic (★★).
Frequency
Consequence
NM_006796.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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AFG3L2 | NM_006796.3 | c.2105G>A | p.Arg702Gln | missense_variant | Exon 16 of 17 | ENST00000269143.8 | NP_006787.2 | |
AFG3L2 | XM_011525601.4 | c.1904G>A | p.Arg635Gln | missense_variant | Exon 15 of 16 | XP_011523903.1 | ||
LOC107985154 | XR_002958227.2 | n.3291+509C>T | intron_variant | Intron 1 of 1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251470Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135908
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461696Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727168
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74374
ClinVar
Submissions by phenotype
not provided Pathogenic:3
Published functional studies suggest a damaging effect as mutant protein in yeast studies is unable to restore endogenous respiration defect (Di Bella et al., 2010); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33726816, 31327635, 34401960, 33598982, 34445196, 20208537) -
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Spinocerebellar ataxia type 28 Pathogenic:2
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at