rs137852627

Positions:

• chr19-17844243-TGGC-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP5

The NM_000215.4(JAK3):​c.172_174del​(p.Ala58del) variant causes a inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 30)
• Consequence: JAK3 NM_000215.4 inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.88

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000215.4. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 19-17844243-TGGC-T is Pathogenic according to our data. Variant chr19-17844243-TGGC-T is described in ClinVar as [Pathogenic]. Clinvar id is 9366.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JAK3	NM_000215.4	c.172_174del	p.Ala58del	inframe_deletion	2/24	ENST00000458235.7
JAK3	XM_011527991.3	c.172_174del	p.Ala58del	inframe_deletion	2/14
JAK3	XM_047438786.1	c.172_174del	p.Ala58del	inframe_deletion	2/24
JAK3	XR_007066796.1	n.222_224del		non_coding_transcript_exon_variant	2/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAK3	ENST00000458235.7	c.172_174del	p.Ala58del	inframe_deletion	2/24	5	NM_000215.4	P1

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

T-B+ severe combined immunodeficiency due to JAK3 deficiency Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 2001

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs137852627; hg19: chr19-17955052;