rs62638624
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PM2PP3PP5_Moderate
The NM_000843.4(GRM6):c.2122C>T(p.Gln708Ter) variant causes a stop gained, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,612,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000843.4 stop_gained, splice_region
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRM6 | NM_000843.4 | c.2122C>T | p.Gln708Ter | stop_gained, splice_region_variant | 9/11 | ENST00000517717.3 | |
ZNF454 | XR_007058600.1 | n.5644-3615G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRM6 | ENST00000517717.3 | c.2122C>T | p.Gln708Ter | stop_gained, splice_region_variant | 9/11 | 5 | NM_000843.4 | P1 | |
ENST00000519491.1 | n.305-3615G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152170Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000724 AC: 18AN: 248740Hom.: 0 AF XY: 0.0000889 AC XY: 12AN XY: 134912
GnomAD4 exome AF: 0.0000390 AC: 57AN: 1460820Hom.: 0 Cov.: 33 AF XY: 0.0000427 AC XY: 31AN XY: 726652
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152170Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74324
ClinVar
Submissions by phenotype
not provided Pathogenic:1Other:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 17, 2023 | This sequence change creates a premature translational stop signal (p.Gln708*) in the GRM6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GRM6 are known to be pathogenic (PMID: 15781871, 16622103, 22008250). This variant is present in population databases (rs62638624, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with congenital stationary night blindness (PMID: 15781871, 22008250). ClinVar contains an entry for this variant (Variation ID: 5842). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. - |
not provided, no classification provided | literature only | Retina International | - | - - |
Congenital stationary night blindness 1B Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 29, 2005 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at