rs13420683

Positions:

• chr2-97719889-C-A
• chr2-97719889-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000264972.10(ZAP70):​c.-21-4127C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,920 control chromosomes in the GnomAD database, including 14,110 homozygotes. 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: 𝑓 0.38 (14110 hom., cov: 31)
• Consequence: ZAP70 ENST00000264972.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02

Genes affected

ZAP70 (HGNC:12858): (zeta chain of T cell receptor associated protein kinase 70) This gene encodes an enzyme belonging to the protein tyrosine kinase family, and it plays a role in T-cell development and lymphocyte activation. This enzyme, which is phosphorylated on tyrosine residues upon T-cell antigen receptor (TCR) stimulation, functions in the initial step of TCR-mediated signal transduction in combination with the Src family kinases, Lck and Fyn. This enzyme is also essential for thymocyte development. Mutations in this gene cause selective T-cell defect, a severe combined immunodeficiency disease characterized by a selective absence of CD8-positive T-cells. Two transcript variants that encode different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZAP70	NM_001079.4	c.-21-4127C>A		intron_variant		ENST00000264972.10	NP_001070.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZAP70	ENST00000264972.10	c.-21-4127C>A		intron_variant		1	NM_001079.4	ENSP00000264972	P1
ZAP70	ENST00000698508.1	c.-21-4127C>A		intron_variant				ENSP00000513759	P1
ZAP70	ENST00000483781.5	n.173-4127C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57836 AN: 151802 Hom.: 14075 Cov.: 31

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.381 AC: 57917 AN: 151920 Hom.: 14110 Cov.: 31 AF XY: 0.372 AC XY: 27607 AN XY: 74284

Gnomad4 AFR AF: 0.692

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.394

Alfa AF: 0.296 Hom.: 6294

Bravo AF: 0.409

Asia WGS AF: 0.188 AC: 656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.8
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs13420683; hg19: chr2-98336352;