rs753473919
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003331.5(TYK2):c.80G>A(p.Gly27Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,460,494 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G27V) has been classified as Uncertain significance.
Frequency
Consequence
NM_003331.5 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 | UniProt |
---|---|---|---|---|---|---|---|
TYK2 | NM_003331.5 | c.80G>A | p.Gly27Asp | missense_variant | 3/25 | ENST00000525621.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TYK2 | ENST00000525621.6 | c.80G>A | p.Gly27Asp | missense_variant | 3/25 | 1 | NM_003331.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1460494Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 726544
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Immunodeficiency 35 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 10, 2018 | Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This sequence change replaces glycine with aspartic acid at codon 27 of the TYK2 protein (p.Gly27Asp). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TYK2-related disease. 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