chr13-110651040-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_024537.4(CARS2):c.1048C>G(p.Arg350Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000959 in 1,460,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R350C) has been classified as Uncertain significance.
Frequency
Consequence
NM_024537.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CARS2 | NM_024537.4 | c.1048C>G | p.Arg350Gly | missense_variant | 10/15 | ENST00000257347.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CARS2 | ENST00000257347.9 | c.1048C>G | p.Arg350Gly | missense_variant | 10/15 | 1 | NM_024537.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.0000240 AC: 6AN: 249612Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135390
GnomAD4 exome AF: 0.00000959 AC: 14AN: 1460454Hom.: 0 Cov.: 29 AF XY: 0.00000826 AC XY: 6AN XY: 726554
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Combined oxidative phosphorylation defect type 27 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2022 | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 350 of the CARS2 protein (p.Arg350Gly). This variant is present in population databases (rs773231493, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of CARS2-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 475613). 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 09, 2021 | The c.1048C>G (p.R350G) alteration is located in exon 10 (coding exon 10) of the CARS2 gene. This alteration results from a C to G substitution at nucleotide position 1048, causing the arginine (R) at amino acid position 350 to be replaced by a glycine (G). 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