19-10378364-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_003331.5(TYK2):c.43G>A(p.Val15Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,612,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. V15A) has been classified as Likely benign.
Frequency
Consequence
NM_003331.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TYK2 | NM_003331.5 | c.43G>A | p.Val15Ile | missense_variant | 3/25 | ENST00000525621.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TYK2 | ENST00000525621.6 | c.43G>A | p.Val15Ile | missense_variant | 3/25 | 1 | NM_003331.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000563 AC: 14AN: 248758Hom.: 0 AF XY: 0.0000518 AC XY: 7AN XY: 135190
GnomAD4 exome AF: 0.0000507 AC: 74AN: 1459996Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 39AN XY: 726306
GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74316
ClinVar
Submissions by phenotype
Immunodeficiency 35 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 04, 2022 | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 15 of the TYK2 protein (p.Val15Ile). This variant is present in population databases (rs374780145, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TYK2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). 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