19-17837150-C-T
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong
The NM_000215.4(JAK3):c.1765G>A(p.Gly589Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000355 in 1,407,352 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 Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. G589G) has been classified as Likely pathogenic.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000036 ( 0 hom. )
Consequence
JAK3
NM_000215.4 missense
NM_000215.4 missense
Scores
14
4
Clinical Significance
Conservation
PhyloP100: 7.20
Publications
7 publications found
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]
JAK3 Gene-Disease associations (from GenCC):
- T-B+ severe combined immunodeficiency due to JAK3 deficiencyInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, ClinGen, Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 14 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.991
PP5
Variant 19-17837150-C-T is Pathogenic according to our data. Variant chr19-17837150-C-T is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 265205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000215.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| JAK3 | NM_000215.4 | MANE Select | c.1765G>A | p.Gly589Ser | missense | Exon 13 of 24 | NP_000206.2 | ||
| JAK3 | NM_001440439.1 | c.1765G>A | p.Gly589Ser | missense | Exon 13 of 24 | NP_001427368.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| JAK3 | ENST00000458235.7 | TSL:5 MANE Select | c.1765G>A | p.Gly589Ser | missense | Exon 13 of 24 | ENSP00000391676.1 | ||
| JAK3 | ENST00000527670.5 | TSL:1 | c.1765G>A | p.Gly589Ser | missense | Exon 12 of 23 | ENSP00000432511.1 | ||
| JAK3 | ENST00000534444.1 | TSL:1 | c.1765G>A | p.Gly589Ser | missense | Exon 13 of 23 | ENSP00000436421.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000577 AC: 1AN: 173398 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
173398
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000355 AC: 5AN: 1407352Hom.: 0 Cov.: 32 AF XY: 0.00000288 AC XY: 2AN XY: 695120 show subpopulations
GnomAD4 exome
AF:
AC:
5
AN:
1407352
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
695120
show subpopulations
African (AFR)
AF:
AC:
0
AN:
32136
American (AMR)
AF:
AC:
0
AN:
37308
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25252
East Asian (EAS)
AF:
AC:
1
AN:
36702
South Asian (SAS)
AF:
AC:
0
AN:
79706
European-Finnish (FIN)
AF:
AC:
0
AN:
49500
Middle Eastern (MID)
AF:
AC:
0
AN:
4210
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1084286
Other (OTH)
AF:
AC:
0
AN:
58252
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.405
Heterozygous variant carriers
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0
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2
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic/Likely pathogenic
Revision:criteria provided, multiple submitters, no conflicts