NM_000215.4:c.*1835G>C

Variant names:

• chr19-17824908-C-G
• rs990232897
• NM_000215.4:c.*1835G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000215.4(JAK3):​c.*1835G>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 0.0000152 in 65,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: JAK3 NM_000215.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647
• Publications: 0 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 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, ClinGen, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAK3	NM_000215.4	c.*1835G>C		3_prime_UTR_variant	Exon 24 of 24	ENST00000458235.7	NP_000206.2
JAK3	NM_001440439.1	c.*1835G>C		3_prime_UTR_variant	Exon 24 of 24		NP_001427368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JAK3	ENST00000458235.7	c.*1835G>C		3_prime_UTR_variant	Exon 24 of 24	5	NM_000215.4	ENSP00000391676.1
JAK3	ENST00000527031.5	n.2681G>C		non_coding_transcript_exon_variant	Exon 14 of 14	2
JAK3	ENST00000696967.1	n.4387G>C		non_coding_transcript_exon_variant	Exon 19 of 19
JAK3	ENST00000696968.1	n.*39G>C		downstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000152 AC: 1 AN: 65928 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 30704

African (AFR) AF: 0.00 AC: 0 AN: 2976

American (AMR) AF: 0.00 AC: 0 AN: 1952

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4222

East Asian (EAS) AF: 0.00 AC: 0 AN: 9662

South Asian (SAS) AF: 0.00 AC: 0 AN: 566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 60

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 400

European-Non Finnish (NFE) AF: 0.0000247 AC: 1 AN: 40544

Other (OTH) AF: 0.00 AC: 0 AN: 5546

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.58
DANN	Benign	0.67
PhyloP100		-0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs990232897; hg19: chr19-17935717;