NM_000215.4:c.*1319G>A

Variant names:

• chr19-17825424-C-T
• rs118101939
• NM_000215.4:c.*1319G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000215.4(JAK3):​c.*1319G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 218,150 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (29 hom., cov: 32)
  • Exomes 𝑓: 0.012 (6 hom.)
• Consequence: JAK3 NM_000215.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.54
• Publications: 5 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, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-17825424-C-T is Benign according to our data. Variant chr19-17825424-C-T is described in ClinVar as Benign. ClinVar VariationId is 891136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0138 (2098/152160) while in subpopulation NFE AF = 0.0215 (1465/67996). AF 95% confidence interval is 0.0206. There are 29 homozygotes in GnomAd4. There are 959 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 29 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000215.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAK3	NM_000215.4	MANE Select	c.*1319G>A		3_prime_UTR	Exon 24 of 24	NP_000206.2
	JAK3	NM_001440439.1		c.*1319G>A		3_prime_UTR	Exon 24 of 24	NP_001427368.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAK3	ENST00000458235.7	TSL:5 MANE Select	c.*1319G>A		3_prime_UTR	Exon 24 of 24	ENSP00000391676.1	P52333-1
	JAK3	ENST00000696967.1		n.3871G>A		non_coding_transcript_exon	Exon 19 of 19
	JAK3	ENST00000696968.1		n.1927G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 2098 AN: 152042 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.00447

Gnomad AMI AF: 0.0407

Gnomad AMR AF: 0.00833

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0215

Gnomad OTH AF: 0.00669

GnomAD4 exome AF: 0.0123 AC: 814 AN: 65990 Hom.: 6 Cov.: 0 AF XY: 0.0125 AC XY: 384 AN XY: 30620

African (AFR) AF: 0.00201 AC: 6 AN: 2992

American (AMR) AF: 0.00725 AC: 14 AN: 1930

Ashkenazi Jewish (ASJ) AF: 0.00429 AC: 18 AN: 4196

East Asian (EAS) AF: 0.00 AC: 0 AN: 9672

South Asian (SAS) AF: 0.00172 AC: 1 AN: 580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52

Middle Eastern (MID) AF: 0.00248 AC: 1 AN: 404

European-Non Finnish (NFE) AF: 0.0175 AC: 713 AN: 40628

Other (OTH) AF: 0.0110 AC: 61 AN: 5536

GnomAD4 genome AF: 0.0138 AC: 2098 AN: 152160 Hom.: 29 Cov.: 32 AF XY: 0.0129 AC XY: 959 AN XY: 74386

African (AFR) AF: 0.00446 AC: 185 AN: 41518

American (AMR) AF: 0.00832 AC: 127 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00605 AC: 21 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00352 AC: 17 AN: 4824

European-Finnish (FIN) AF: 0.0219 AC: 232 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0215 AC: 1465 AN: 67996

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.0145 Hom.: 2

Bravo AF: 0.0125

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	T-B+ severe combined immunodeficiency due to JAK3 deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.30
DANN	Benign	0.59
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism

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: rs118101939; hg19: chr19-17936233;