rs13420683

Variant names:

• chr2-97719889-C-A
• rs13420683
• NM_001079.4:c.-21-4127C>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001079.4(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 NM_001079.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02
• Publications: 11 publications found

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]

ZAP70 Gene-Disease associations (from GenCC):

• combined immunodeficiency due to ZAP70 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZAP70	NM_001079.4	MANE Select	c.-21-4127C>A		intron	N/A	NP_001070.2
	ZAP70	NM_001378594.1		c.-21-4127C>A		intron	N/A	NP_001365523.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZAP70	ENST00000264972.10	TSL:1 MANE Select	c.-21-4127C>A		intron	N/A	ENSP00000264972.5
	ZAP70	ENST00000698508.2		c.-21-4127C>A		intron	N/A	ENSP00000513759.1
	ZAP70	ENST00000483781.5	TSL:2	n.173-4127C>A		intron	N/A

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

African (AFR) AF: 0.692 AC: 28601 AN: 41340

American (AMR) AF: 0.271 AC: 4142 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1057 AN: 3468

East Asian (EAS) AF: 0.227 AC: 1171 AN: 5158

South Asian (SAS) AF: 0.116 AC: 561 AN: 4816

European-Finnish (FIN) AF: 0.161 AC: 1703 AN: 10592

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19456 AN: 67956

Other (OTH) AF: 0.394 AC: 830 AN: 2108

Alfa AF: 0.315 Hom.: 11199

Bravo AF: 0.409

Asia WGS AF: 0.188 AC: 656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.8
DANN	Benign	0.43
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13420683; hg19: chr2-98336352;