19-17831723-G-C

Position:

• chr19-17831723-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000215.4(JAK3):​c.2756C>G​(p.Ala919Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: JAK3 NM_000215.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.090759605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAK3	NM_000215.4	c.2756C>G	p.Ala919Gly	missense_variant	20/24	ENST00000458235.7	NP_000206.2
JAK3	XM_047438786.1	c.2756C>G	p.Ala919Gly	missense_variant	20/24		XP_047294742.1
JAK3	XR_007066796.1	n.2891C>G		splice_region_variant, non_coding_transcript_exon_variant	20/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAK3	ENST00000458235.7	c.2756C>G	p.Ala919Gly	missense_variant	20/24	5	NM_000215.4	ENSP00000391676.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.38	T;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.66	T;.;T
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.091	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.13	N;N;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.86	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.37	T;T;T
Sift4G	Benign	0.39	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.25
MutPred		0.32		Loss of stability (P = 0.0318);Loss of stability (P = 0.0318);Loss of stability (P = 0.0318);
MVP		0.68
MPC		0.48
ClinPred		0.080	T
GERP RS		1.6
Varity_R		0.19
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-17942532;