5-150297293-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.1631G>A(p.Arg544His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000299 in 1,609,840 control chromosomes in the GnomAD database, including 1 homozygotes. 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 (★★).
Frequency
Consequence
NM_001012301.4 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 |
---|---|---|---|---|---|---|---|
ARSI | NM_001012301.4 | c.1631G>A | p.Arg544His | missense_variant | 2/2 | ENST00000328668.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARSI | ENST00000328668.8 | c.1631G>A | p.Arg544His | missense_variant | 2/2 | 1 | NM_001012301.4 | P1 | |
ARSI | ENST00000515301.2 | c.1202G>A | p.Arg401His | missense_variant | 2/2 | 4 |
Frequencies
GnomAD3 genomes AF: 0.000177 AC: 27AN: 152144Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000113 AC: 28AN: 247722Hom.: 0 AF XY: 0.0000971 AC XY: 13AN XY: 133918
GnomAD4 exome AF: 0.000311 AC: 454AN: 1457696Hom.: 1 Cov.: 29 AF XY: 0.000284 AC XY: 206AN XY: 725122
GnomAD4 genome AF: 0.000177 AC: 27AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15AN XY: 74334
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 03, 2022 | The c.1631G>A (p.R544H) 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 1631, causing the arginine (R) at amino acid position 544 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 12, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 544 of the ARSI protein (p.Arg544His). 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 output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 661582). This variant has not been reported in the literature in individuals affected with ARSI-related conditions. This variant is present in population databases (rs763136370, gnomAD 0.02%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at