rs104893740
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_144499.3(GNAT1):c.113G>A(p.Gly38Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,700 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 Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
GNAT1
NM_144499.3 missense
NM_144499.3 missense
Scores
14
3
1
Clinical Significance
Conservation
PhyloP100: 9.59
Genes affected
GNAT1 (HGNC:4393): (G protein subunit alpha transducin 1) Transducin is a 3-subunit guanine nucleotide-binding protein (G protein) which stimulates the coupling of rhodopsin and cGMP-phoshodiesterase during visual impulses. The transducin alpha subunits in rods and cones are encoded by separate genes. This gene encodes the alpha subunit in rods. This gene is also expressed in other cells, and has been implicated in bitter taste transduction in rat taste cells. Mutations in this gene result in autosomal dominant congenital stationary night blindness. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Feb 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.98
PP5
?
Variant 3-50193139-G-A is Pathogenic according to our data. Variant chr3-50193139-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 15926.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-50193139-G-A is described in Lovd as [Likely_pathogenic]. Variant chr3-50193139-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNAT1 | NM_144499.3 | c.113G>A | p.Gly38Asp | missense_variant | 2/9 | ENST00000232461.8 | |
GNAT1 | NM_000172.4 | c.113G>A | p.Gly38Asp | missense_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNAT1 | ENST00000232461.8 | c.113G>A | p.Gly38Asp | missense_variant | 2/9 | 5 | NM_144499.3 | P1 | |
GNAT1 | ENST00000433068.5 | c.113G>A | p.Gly38Asp | missense_variant | 2/9 | 5 | P1 | ||
GNAT1 | ENST00000440836.1 | c.-32G>A | 5_prime_UTR_variant | 2/5 | 3 | ||||
GNAT1 | ENST00000467787.1 | n.294G>A | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251172Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135862
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461700Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727186
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
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ExAC
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Congenital stationary night blindness autosomal dominant 3 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 1996 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;H
MutationTaster
Benign
A;A
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Loss of catalytic residue at G38 (P = 0.0399);Loss of catalytic residue at G38 (P = 0.0399);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at