rs144360023
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001079.4(ZAP70):c.594C>T(p.Tyr198=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,614,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
ZAP70
NM_001079.4 synonymous
NM_001079.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.91
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]
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ACMG classification
Classification made for transcript
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=-0.69).
BP6
?
Variant 2-97732913-C-T is Benign according to our data. Variant chr2-97732913-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 538575.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-3.91 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZAP70 | NM_001079.4 | c.594C>T | p.Tyr198= | synonymous_variant | 5/14 | ENST00000264972.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZAP70 | ENST00000264972.10 | c.594C>T | p.Tyr198= | synonymous_variant | 5/14 | 1 | NM_001079.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152238Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000875 AC: 22AN: 251308Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135874
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GnomAD4 exome AF: 0.000105 AC: 154AN: 1461672Hom.: 0 Cov.: 31 AF XY: 0.0000990 AC XY: 72AN XY: 727160
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GnomAD4 genome ? AF: 0.000138 AC: 21AN: 152356Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74502
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
ZAP70-Related Severe Combined Immunodeficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 27, 2023 | - - |
Computational scores
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Benign
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Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at