rs774941503
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3
The NM_000215.4(JAK3):c.446G>C(p.Arg149Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,904 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R149S) has been classified as Uncertain significance.
Frequency
Consequence
NM_000215.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JAK3 | NM_000215.4 | c.446G>C | p.Arg149Pro | missense_variant | 5/24 | ENST00000458235.7 | |
JAK3 | XM_047438786.1 | c.446G>C | p.Arg149Pro | missense_variant | 5/24 | ||
JAK3 | XM_011527991.3 | c.446G>C | p.Arg149Pro | missense_variant | 5/14 | ||
JAK3 | XR_007066796.1 | n.496G>C | non_coding_transcript_exon_variant | 5/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JAK3 | ENST00000458235.7 | c.446G>C | p.Arg149Pro | missense_variant | 5/24 | 5 | NM_000215.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.87e-7 AC: 1AN: 1454904Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 723918
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
T-B+ severe combined immunodeficiency due to JAK3 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 22, 2018 | This variant has not been reported in the literature in individuals with JAK3-related disease. This sequence change replaces arginine with proline at codon 149 of the JAK3 protein (p.Arg149Pro). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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