rs3212780
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The ENST00000534444.1(JAK3):c.3282C>T(p.Ala1094=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,056,466 control chromosomes in the GnomAD database, including 34,324 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.20 ( 3927 hom., cov: 32)
Exomes 𝑓: 0.25 ( 30397 hom. )
Consequence
JAK3
ENST00000534444.1 synonymous
ENST00000534444.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.69
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 19-17830033-G-A is Benign according to our data. Variant chr19-17830033-G-A is described in ClinVar as [Benign]. Clinvar id is 1283176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-17830033-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-2.68 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JAK3 | NM_000215.4 | c.3207+75C>T | intron_variant | ENST00000458235.7 | |||
JAK3 | XM_047438786.1 | c.3207+75C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JAK3 | ENST00000458235.7 | c.3207+75C>T | intron_variant | 5 | NM_000215.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.205 AC: 31159AN: 152080Hom.: 3929 Cov.: 32
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GnomAD3 exomes AF: 0.212 AC: 29325AN: 138050Hom.: 3672 AF XY: 0.216 AC XY: 16257AN XY: 75296
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GnomAD4 exome AF: 0.250 AC: 225729AN: 904268Hom.: 30397 Cov.: 12 AF XY: 0.248 AC XY: 115322AN XY: 464788
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GnomAD4 genome ? AF: 0.205 AC: 31157AN: 152198Hom.: 3927 Cov.: 32 AF XY: 0.207 AC XY: 15381AN XY: 74408
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jan 24, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 28% of patients studied by a panel of primary immunodeficiencies. Number of patients: 25. Only high quality variants are reported. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 25, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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