rs56340622
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001079.4(ZAP70):c.672C>T(p.Pro224=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,614,134 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.010 ( 28 hom., cov: 33)
Exomes 𝑓: 0.00097 ( 21 hom. )
Consequence
ZAP70
NM_001079.4 synonymous
NM_001079.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -5.78
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 Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 2-97732991-C-T is Benign according to our data. Variant chr2-97732991-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 337631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-5.78 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0103 (1573/152354) while in subpopulation AFR AF= 0.0355 (1475/41568). AF 95% confidence interval is 0.034. There are 28 homozygotes in gnomad4. There are 737 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 28 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZAP70 | NM_001079.4 | c.672C>T | p.Pro224= | synonymous_variant | 5/14 | ENST00000264972.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZAP70 | ENST00000264972.10 | c.672C>T | p.Pro224= | synonymous_variant | 5/14 | 1 | NM_001079.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0103 AC: 1572AN: 152236Hom.: 28 Cov.: 33
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GnomAD3 exomes AF: 0.00280 AC: 705AN: 251408Hom.: 12 AF XY: 0.00208 AC XY: 282AN XY: 135898
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GnomAD4 exome AF: 0.000967 AC: 1414AN: 1461780Hom.: 21 Cov.: 31 AF XY: 0.000793 AC XY: 577AN XY: 727208
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GnomAD4 genome AF: 0.0103 AC: 1573AN: 152354Hom.: 28 Cov.: 33 AF XY: 0.00989 AC XY: 737AN XY: 74504
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
ZAP70-Related Severe Combined Immunodeficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Combined immunodeficiency due to ZAP70 deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at