rs6712517

Variant names:

• chr2-97723901-A-C
• rs6712517
• NM_001079.4:c.-21-115A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-97723901-A-C
• chr2-97723901-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001079.4(ZAP70):​c.-21-115A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 1,185,398 control chromosomes in the GnomAD database, including 321,744 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (46342 hom., cov: 35)
  • Exomes 𝑓: 0.72 (275402 hom.)
• Consequence: ZAP70 NM_001079.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.58
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 2-97723901-A-C is Benign according to our data. Variant chr2-97723901-A-C is described in ClinVar as Benign. ClinVar VariationId is 1229846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.909 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZAP70	NM_001079.4	MANE Select	c.-21-115A>C		intron	N/A	NP_001070.2
	ZAP70	NM_001378594.1		c.-21-115A>C		intron	N/A	NP_001365523.1	P43403-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZAP70	ENST00000264972.10	TSL:1 MANE Select	c.-21-115A>C		intron	N/A	ENSP00000264972.5	P43403-1
	ZAP70	ENST00000698508.2		c.-21-115A>C		intron	N/A	ENSP00000513759.1	P43403-1
	ZAP70	ENST00000885386.1		c.-21-115A>C		intron	N/A	ENSP00000555445.1

Frequencies

GnomAD3 genomes AF: 0.770 AC: 117112 AN: 152150 Hom.: 46288 Cov.: 35

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.921

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.774

GnomAD4 exome AF: 0.721 AC: 744432 AN: 1033130 Hom.: 275402 AF XY: 0.708 AC XY: 364073 AN XY: 513866

African (AFR) AF: 0.925 AC: 22629 AN: 24456

American (AMR) AF: 0.658 AC: 19104 AN: 29018

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 13057 AN: 19514

East Asian (EAS) AF: 0.481 AC: 16183 AN: 33670

South Asian (SAS) AF: 0.358 AC: 22727 AN: 63544

European-Finnish (FIN) AF: 0.756 AC: 23743 AN: 31420

Middle Eastern (MID) AF: 0.699 AC: 2273 AN: 3250

European-Non Finnish (NFE) AF: 0.757 AC: 592386 AN: 782470

Other (OTH) AF: 0.706 AC: 32330 AN: 45788

GnomAD4 genome AF: 0.770 AC: 117217 AN: 152268 Hom.: 46342 Cov.: 35 AF XY: 0.762 AC XY: 56695 AN XY: 74438

African (AFR) AF: 0.916 AC: 38112 AN: 41590

American (AMR) AF: 0.695 AC: 10635 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2365 AN: 3472

East Asian (EAS) AF: 0.499 AC: 2570 AN: 5154

South Asian (SAS) AF: 0.341 AC: 1648 AN: 4826

European-Finnish (FIN) AF: 0.749 AC: 7938 AN: 10600

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.754 AC: 51260 AN: 68002

Other (OTH) AF: 0.767 AC: 1623 AN: 2116

Alfa AF: 0.763 Hom.: 115211

Bravo AF: 0.783

Asia WGS AF: 0.456 AC: 1586 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.68
DANN	Benign	0.59
PhyloP100		-1.6
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: rs6712517; hg19: chr2-98340364;