rs773316961
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2
The ENST00000389266.8(GARS1):c.1817G>A(p.Ser606Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,612,580 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S606T) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000389266.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GARS1 | NM_002047.4 | c.1817G>A | p.Ser606Asn | missense_variant | 15/17 | ENST00000389266.8 | NP_002038.2 | |
GARS1 | NM_001316772.1 | c.1655G>A | p.Ser552Asn | missense_variant | 15/17 | NP_001303701.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GARS1 | ENST00000389266.8 | c.1817G>A | p.Ser606Asn | missense_variant | 15/17 | 1 | NM_002047.4 | ENSP00000373918 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152084Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000281 AC: 7AN: 248980Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 135184
GnomAD4 exome AF: 0.00000959 AC: 14AN: 1460496Hom.: 0 Cov.: 29 AF XY: 0.0000110 AC XY: 8AN XY: 726650
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152084Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74248
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 20, 2022 | This variant has not been reported in the literature in individuals affected with GARS-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GARS protein function. ClinVar contains an entry for this variant (Variation ID: 543238). This variant is present in population databases (rs773316961, gnomAD 0.006%). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 606 of the GARS protein (p.Ser606Asn). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2022 | GARS1: BS2 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at