rs201101011
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_000215.4(JAK3):c.630G>A(p.Arg210=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000592 in 1,587,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000060 ( 0 hom. )
Consequence
JAK3
NM_000215.4 synonymous
NM_000215.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.90
Genes affected
JAK3 (HGNC:6193): (Janus kinase 3) The protein encoded by this gene is a member of the Janus kinase (JAK) family of tyrosine kinases involved in cytokine receptor-mediated intracellular signal transduction. It is predominantly expressed in immune cells and transduces a signal in response to its activation via tyrosine phosphorylation by interleukin receptors. Mutations in this gene are associated with autosomal SCID (severe combined immunodeficiency disease). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
Variant 19-17842547-C-T is Benign according to our data. Variant chr19-17842547-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 532753.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-1.9 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JAK3 | NM_000215.4 | c.630G>A | p.Arg210= | synonymous_variant | 6/24 | ENST00000458235.7 | |
JAK3 | XM_047438786.1 | c.630G>A | p.Arg210= | synonymous_variant | 6/24 | ||
JAK3 | XM_011527991.3 | c.630G>A | p.Arg210= | synonymous_variant | 6/14 | ||
JAK3 | XR_007066796.1 | n.680G>A | non_coding_transcript_exon_variant | 6/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JAK3 | ENST00000458235.7 | c.630G>A | p.Arg210= | synonymous_variant | 6/24 | 5 | NM_000215.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000525 AC: 8AN: 152242Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000860 AC: 17AN: 197696Hom.: 0 AF XY: 0.0000649 AC XY: 7AN XY: 107838
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GnomAD4 exome AF: 0.0000599 AC: 86AN: 1435480Hom.: 0 Cov.: 37 AF XY: 0.0000534 AC XY: 38AN XY: 711948
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GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152360Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74506
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
T-B+ severe combined immunodeficiency due to JAK3 deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 11, 2022 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at