5-178991554-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2PM5BP4_Moderate
The NM_000843.4(GRM6):āc.727G>Cā(p.Val243Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,612,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V243F) has been classified as Likely benign.
Frequency
Consequence
NM_000843.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GRM6 | NM_000843.4 | c.727G>C | p.Val243Leu | missense_variant | 4/11 | ENST00000517717.3 | NP_000834.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GRM6 | ENST00000517717.3 | c.727G>C | p.Val243Leu | missense_variant | 4/11 | 5 | NM_000843.4 | ENSP00000430767 | P1 | |
GRM6 | ENST00000231188.9 | c.727G>C | p.Val243Leu | missense_variant | 3/10 | 2 | ENSP00000231188 | P1 | ||
GRM6 | ENST00000650031.1 | c.727G>C | p.Val243Leu | missense_variant | 5/12 | ENSP00000497110 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 151958Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251300Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135838
GnomAD4 exome AF: 0.00000822 AC: 12AN: 1460720Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8AN XY: 726714
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152074Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74370
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 12, 2022 | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 243 of the GRM6 protein (p.Val243Leu). This variant is present in population databases (rs17078894, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with GRM6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1053686). 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 GRM6 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