Variant chr19-17826620-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000215.4(JAK3):c.*123T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 1,054,640 control chromosomes in the GnomAD database, including 126,994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 21277 hom., cov: 31)

Exomes 𝑓: 0.48 ( 105717 hom. )

Consequence

JAK3
NM_000215.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.568

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 19-17826620-A-G is Benign according to our data. Variant chr19-17826620-A-G is described in ClinVar as [Benign]. Clinvar id is 328495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAK3	NM_000215.4 linkuse as main transcript	c.*123T>C		3_prime_UTR_variant	24/24	ENST00000458235.7	NP_000206.2
JAK3	XM_047438786.1 linkuse as main transcript	c.*123T>C		3_prime_UTR_variant	24/24		XP_047294742.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAK3	ENST00000458235.7 linkuse as main transcript	c.*123T>C		3_prime_UTR_variant	24/24	5	NM_000215.4	ENSP00000391676	P1	P52333-1

Frequencies

GnomAD3 genomes

AF:

0.522

AC:

79281

AN:

151812

Hom.:

21246

Cov.:

show subpopulations

Gnomad AFR

AF:

0.634

Gnomad AMI

AF:

0.445

Gnomad AMR

AF:

0.529

Gnomad ASJ

AF:

0.504

Gnomad EAS

AF:

0.453

Gnomad SAS

AF:

0.477

Gnomad FIN

AF:

0.509

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.466

Gnomad OTH

AF:

0.522

GnomAD4 exome

AF:

0.482

AC:

435176

AN:

902710

Hom.:

105717

Cov.:

AF XY:

0.480

AC XY:

226447

AN XY:

471464

show subpopulations

Gnomad4 AFR exome

AF:

0.643

Gnomad4 AMR exome

AF:

0.591

Gnomad4 ASJ exome

AF:

0.502

Gnomad4 EAS exome

AF:

0.451

Gnomad4 SAS exome

AF:

0.484

Gnomad4 FIN exome

AF:

0.519

Gnomad4 NFE exome

AF:

0.465

Gnomad4 OTH exome

AF:

0.492

GnomAD4 genome

AF:

0.522

AC:

79369

AN:

151930

Hom.:

21277

Cov.:

AF XY:

0.523

AC XY:

38831

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.634

Gnomad4 AMR

AF:

0.530

Gnomad4 ASJ

AF:

0.504

Gnomad4 EAS

AF:

0.452

Gnomad4 SAS

AF:

0.477

Gnomad4 FIN

AF:

0.509

Gnomad4 NFE

AF:

0.466

Gnomad4 OTH

AF:

0.521

Alfa

AF:

0.493

Hom.:

10293

Bravo

AF:

0.531

Asia WGS

AF:

0.498

AC:

1732

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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 20% of patients studied by a panel of primary immunodeficiencies. Number of patients: 18. Only high quality variants are reported. -

T-B+ severe combined immunodeficiency due to JAK3 deficiency

Benign:1

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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.0

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over