chr19-17838361-C-T

Variant names:

• chr19-17838361-C-T
• NM_000215.4:c.1471G>A

Variant summary

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

The NM_000215.4(JAK3):​c.1471G>A​(p.Gly491Ser) 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. 16/21 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: 31)
• Consequence: JAK3 NM_000215.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.68

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.086129695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAK3	NM_000215.4	c.1471G>A	p.Gly491Ser	missense_variant	Exon 11 of 24	ENST00000458235.7	NP_000206.2
JAK3	XM_047438786.1	c.1471G>A	p.Gly491Ser	missense_variant	Exon 11 of 24		XP_047294742.1
JAK3	XM_011527991.3	c.1471G>A	p.Gly491Ser	missense_variant	Exon 11 of 14		XP_011526293.2
JAK3	XR_007066796.1	n.1521G>A		non_coding_transcript_exon_variant	Exon 11 of 20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JAK3	ENST00000458235.7	c.1471G>A	p.Gly491Ser	missense_variant	Exon 11 of 24	5	NM_000215.4	ENSP00000391676.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.0064	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	11
DANN	Benign	0.87
DEOGEN2	Benign	0.20	T;T;.
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.71	T;.;T
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.086	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.2	L;L;L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.73	N;N;N
REVEL	Benign	0.23
Sift	Benign	0.17	T;T;T
Sift4G	Benign	0.38	T;T;T
Polyphen		0.0020	B;B;B
Vest4		0.11
MutPred		0.24		Gain of disorder (P = 0.0375);Gain of disorder (P = 0.0375);Gain of disorder (P = 0.0375);
MVP		0.73
MPC		0.48
ClinPred		0.24	T
GERP RS		4.7
Varity_R		0.099
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr19-17949170; COSMIC: COSV71686538; COSMIC: COSV71686538;