NM_004446.3:c.4441A>G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_004446.3(EPRS1):c.4441A>G(p.Ile1481Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000886 in 1,614,076 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 (★).
Frequency
Consequence
NM_004446.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000506 AC: 77AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000167 AC: 42AN: 250894Hom.: 0 AF XY: 0.0000737 AC XY: 10AN XY: 135698
GnomAD4 exome AF: 0.0000452 AC: 66AN: 1461766Hom.: 0 Cov.: 32 AF XY: 0.0000344 AC XY: 25AN XY: 727196
GnomAD4 genome AF: 0.000506 AC: 77AN: 152310Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25AN XY: 74480
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1481 of the EPRS protein (p.Ile1481Val). This variant is present in population databases (rs35055527, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with EPRS-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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