2-97724084-G-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001079.4(ZAP70):c.48G>C(p.Ser16=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. S16S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZAP70 NM_001079.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0740

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 Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 2-97724084-G-C is Benign according to our data. Variant chr2-97724084-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2061921.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.074 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZAP70	NM_001079.4	c.48G>C	p.Ser16=	synonymous_variant	3/14	ENST00000264972.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZAP70	ENST00000264972.10	c.48G>C	p.Ser16=	synonymous_variant	3/14	1	NM_001079.4	P1
ZAP70	ENST00000698508.1	c.48G>C	p.Ser16=	synonymous_variant	2/13			P1
ZAP70	ENST00000483781.5	n.241G>C		non_coding_transcript_exon_variant	3/7	2
ZAP70	ENST00000698509.1	n.188G>C		non_coding_transcript_exon_variant	1/12

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ZAP70-Related Severe Combined Immunodeficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 05, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	9.2
Dann	Benign	0.89

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-98340547;