rs201576913
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_000215.4(JAK3):c.2451C>T(p.Phe817=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000204 in 1,614,208 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00013 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 2 hom. )
Consequence
JAK3
NM_000215.4 synonymous
NM_000215.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.178
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
Variant 19-17832829-G-A is Benign according to our data. Variant chr19-17832829-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 328504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.178 with no splicing effect.
BS2
?
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JAK3 | NM_000215.4 | c.2451C>T | p.Phe817= | synonymous_variant | 18/24 | ENST00000458235.7 | |
JAK3 | XM_047438786.1 | c.2451C>T | p.Phe817= | synonymous_variant | 18/24 | ||
JAK3 | XR_007066796.1 | n.2501C>T | non_coding_transcript_exon_variant | 18/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JAK3 | ENST00000458235.7 | c.2451C>T | p.Phe817= | synonymous_variant | 18/24 | 5 | NM_000215.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152198Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000426 AC: 107AN: 251418Hom.: 1 AF XY: 0.000574 AC XY: 78AN XY: 135882
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GnomAD4 exome AF: 0.000211 AC: 309AN: 1461892Hom.: 2 Cov.: 33 AF XY: 0.000315 AC XY: 229AN XY: 727246
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GnomAD4 genome ? AF: 0.000131 AC: 20AN: 152316Hom.: 2 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74480
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
T-B+ severe combined immunodeficiency due to JAK3 deficiency Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Centre for Medical Genetics, Mumbai | Aug 14, 2019 | The variant was incidentally detected in an apparently healthy individual of 20 years while performing exome sequencing for indication of previous baby with genodermatoses (icthyosis). - |
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