2-97714363-C-T

Variant names:

• chr2-97714363-C-T
• rs1020396
• NM_001079.4:c.-22+369C>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.-22+369C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,176 control chromosomes in the GnomAD database, including 8,528 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 0.30 (8528 hom., cov: 33)
• Consequence: ZAP70 NM_001079.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZAP70	NM_001079.4	c.-22+369C>T		intron_variant	Intron 2 of 13	ENST00000264972.10	NP_001070.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZAP70	ENST00000264972.10	c.-22+369C>T		intron_variant	Intron 2 of 13	1	NM_001079.4	ENSP00000264972.5
ZAP70	ENST00000698508.2	c.-22+369C>T		intron_variant	Intron 1 of 12			ENSP00000513759.1
ZAP70	ENST00000483781.5	n.172+369C>T		intron_variant	Intron 2 of 6	2
ZAP70	ENST00000718250.1	n.-22+369C>T		intron_variant	Intron 2 of 13			ENSP00000520695.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45714 AN: 152056 Hom.: 8528 Cov.: 33

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.300 AC: 45716 AN: 152176 Hom.: 8528 Cov.: 33 AF XY: 0.304 AC XY: 22590 AN XY: 74426

African (AFR) AF: 0.116 AC: 4809 AN: 41526

American (AMR) AF: 0.246 AC: 3757 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 741 AN: 3466

East Asian (EAS) AF: 0.254 AC: 1315 AN: 5170

South Asian (SAS) AF: 0.139 AC: 668 AN: 4820

European-Finnish (FIN) AF: 0.578 AC: 6126 AN: 10602

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27359 AN: 67980

Other (OTH) AF: 0.256 AC: 541 AN: 2114

Alfa AF: 0.350 Hom.: 8268

Bravo AF: 0.271

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.71
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

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: rs1020396; hg19: chr2-98330826;