chr5-168486505-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_002887.4(RARS1):c.7G>C(p.Val3Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000178 in 1,406,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. V3I) has been classified as Benign.
Frequency
Consequence
NM_002887.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RARS1 | NM_002887.4 | c.7G>C | p.Val3Leu | missense_variant | 1/15 | ENST00000231572.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RARS1 | ENST00000231572.8 | c.7G>C | p.Val3Leu | missense_variant | 1/15 | 1 | NM_002887.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000180 AC: 3AN: 166308Hom.: 0 AF XY: 0.0000114 AC XY: 1AN XY: 87782
GnomAD4 exome AF: 0.0000178 AC: 25AN: 1406510Hom.: 0 Cov.: 45 AF XY: 0.0000202 AC XY: 14AN XY: 694244
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 12, 2023 | The c.7G>C (p.V3L) alteration is located in exon 1 (coding exon 1) of the RARS gene. This alteration results from a G to C substitution at nucleotide position 7, causing the valine (V) at amino acid position 3 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 27, 2022 | This variant is present in population databases (rs244903, gnomAD 0.004%). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with RARS-related conditions. This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 3 of the RARS protein (p.Val3Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at