rs199659429
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_024306.5(FA2H):āc.401T>Gā(p.Val134Gly) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_024306.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FA2H | NM_024306.5 | c.401T>G | p.Val134Gly | missense_variant | Exon 3 of 7 | ENST00000219368.8 | NP_077282.3 | |
FA2H | XM_011523317.4 | c.401T>G | p.Val134Gly | missense_variant | Exon 3 of 6 | XP_011521619.1 | ||
FA2H | XM_011523319.3 | c.161T>G | p.Val54Gly | missense_variant | Exon 3 of 7 | XP_011521621.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FA2H | ENST00000219368.8 | c.401T>G | p.Val134Gly | missense_variant | Exon 3 of 7 | 1 | NM_024306.5 | ENSP00000219368.3 | ||
FA2H | ENST00000569949.1 | c.203T>G | p.Val68Gly | missense_variant | Exon 3 of 5 | 4 | ENSP00000464576.1 | |||
FA2H | ENST00000567683.5 | n.364-8189T>G | intron_variant | Intron 2 of 4 | 2 | ENSP00000455126.1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 1AN: 152156Hom.: 0 Cov.: 33 FAILED QC
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000562 AC: 820AN: 1459712Hom.: 0 Cov.: 32 AF XY: 0.000562 AC XY: 408AN XY: 726136
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000131 AC: 2AN: 152272Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74450
ClinVar
Submissions by phenotype
Spastic paraplegia Uncertain:1
This sequence change replaces valine with glycine at codon 134 of the FA2H protein (p.Val134Gly). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glycine. While this variant is present in population databases (rs199659429), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with a FA2H-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C35"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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