5-150297434-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001012301.4(ARSI):c.1490G>A(p.Arg497His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000218 in 1,608,286 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. R497G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001012301.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ARSI | ENST00000328668.8 | c.1490G>A | p.Arg497His | missense_variant | Exon 2 of 2 | 1 | NM_001012301.4 | ENSP00000333395.7 | ||
ARSI | ENST00000515301.2 | c.1061G>A | p.Arg354His | missense_variant | Exon 2 of 2 | 4 | ENSP00000426879.2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152126Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000610 AC: 15AN: 245830Hom.: 0 AF XY: 0.0000452 AC XY: 6AN XY: 132862
GnomAD4 exome AF: 0.0000227 AC: 33AN: 1456160Hom.: 0 Cov.: 29 AF XY: 0.0000207 AC XY: 15AN XY: 724110
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152126Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74294
ClinVar
Submissions by phenotype
Spastic paraplegia Uncertain:1
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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with ARSI-related conditions. This variant is present in population databases (rs771311478, ExAC 0.02%). This sequence change replaces arginine with histidine at codon 497 of the ARSI protein (p.Arg497His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. -
not specified Uncertain:1
The c.1490G>A (p.R497H) alteration is located in exon 2 (coding exon 2) of the ARSI gene. This alteration results from a G to A substitution at nucleotide position 1490, causing the arginine (R) at amino acid position 497 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at