Variant 2-97737384-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001079.4(ZAP70):c.1290-89C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,419,926 control chromosomes in the GnomAD database, including 83,439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 7351 hom., cov: 32)

Exomes 𝑓: 0.33 ( 76088 hom. )

Consequence

ZAP70
NM_001079.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.64

Variant links:

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 links:

ZAP70 (HGNC:):

ZAP70 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 2-97737384-C-T is Benign according to our data. Variant chr2-97737384-C-T is described in ClinVar as [Benign]. Clinvar id is 1232396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZAP70	NM_001079.4 linkuse as main transcript	c.1290-89C>T		intron_variant		ENST00000264972.10	NP_001070.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZAP70	ENST00000264972.10 linkuse as main transcript	c.1290-89C>T		intron_variant		1	NM_001079.4	ENSP00000264972.5		P43403-1

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42797

AN:

151904

Hom.:

7343

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.426

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.542

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.357

Gnomad OTH

AF:

0.249

GnomAD4 exome

AF:

0.333

AC:

422599

AN:

1267904

Hom.:

76088

AF XY:

0.326

AC XY:

208022

AN XY:

638188

show subpopulations

Gnomad4 AFR exome

AF:

0.116

Gnomad4 AMR exome

AF:

0.379

Gnomad4 ASJ exome

AF:

0.207

Gnomad4 EAS exome

AF:

0.0975

Gnomad4 SAS exome

AF:

0.139

Gnomad4 FIN exome

AF:

0.525

Gnomad4 NFE exome

AF:

0.360

Gnomad4 OTH exome

AF:

0.294

GnomAD4 genome

AF:

0.282

AC:

42814

AN:

152022

Hom.:

7351

Cov.:

AF XY:

0.287

AC XY:

21325

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.125

Gnomad4 AMR

AF:

0.318

Gnomad4 ASJ

AF:

0.188

Gnomad4 EAS

AF:

0.109

Gnomad4 SAS

AF:

0.128

Gnomad4 FIN

AF:

0.542

Gnomad4 NFE

AF:

0.357

Gnomad4 OTH

AF:

0.246

Alfa

AF:

0.319

Hom.:

7957

Bravo

AF:

0.264

Asia WGS

AF:

0.136

AC:

472

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 54% of patients studied by a panel of primary immunodeficiencies. Number of patients: 52. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.13

DANN

Benign

0.38

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over