rs374913800
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_144499.3(GNAT1):c.904C>T(p.Gln302Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000694 in 1,613,818 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 Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_144499.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNAT1 | NM_144499.3 | c.904C>T | p.Gln302Ter | stop_gained | 8/9 | ENST00000232461.8 | |
GNAT1 | NM_000172.4 | c.904C>T | p.Gln302Ter | stop_gained | 8/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNAT1 | ENST00000232461.8 | c.904C>T | p.Gln302Ter | stop_gained | 8/9 | 5 | NM_144499.3 | P1 | |
GNAT1 | ENST00000433068.5 | c.904C>T | p.Gln302Ter | stop_gained | 8/9 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251078Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135828
GnomAD4 exome AF: 0.0000739 AC: 108AN: 1461634Hom.: 0 Cov.: 32 AF XY: 0.0000729 AC XY: 53AN XY: 727124
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74354
ClinVar
Submissions by phenotype
Congenital stationary night blindness 1G Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jul 22, 2024 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 07, 2018 | - - |
not provided Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Mar 09, 2022 | Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 49 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; This variant is associated with the following publications: (PMID: 31589614, 26472407, 27624628, 27977773, 29850563, 26822852, 31736247) - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 16, 2023 | This sequence change creates a premature translational stop signal (p.Gln302*) in the GNAT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GNAT1 are known to be pathogenic (PMID: 11095744, 31736247). This variant is present in population databases (rs374913800, gnomAD 0.005%). This premature translational stop signal has been observed in individual(s) with autosomal recessive retinal dystrophy (PMID: 26472407, 27624628). This variant has been reported in individual(s) with autosomal dominant night blindness (Invitae); however, the role of the variant in this condition is currently unclear. ClinVar contains an entry for this variant (Variation ID: 488669). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at