rs758807149
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_001079.4(ZAP70):c.1415G>A(p.Arg472Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000248 in 1,613,962 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R472R) has been classified as Likely benign.
Frequency
Consequence
NM_001079.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZAP70 | NM_001079.4 | c.1415G>A | p.Arg472Gln | missense_variant | 11/14 | ENST00000264972.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZAP70 | ENST00000264972.10 | c.1415G>A | p.Arg472Gln | missense_variant | 11/14 | 1 | NM_001079.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152128Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000597 AC: 15AN: 251202Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135788
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461834Hom.: 1 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 727226
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74302
ClinVar
Submissions by phenotype
ZAP70-Related Severe Combined Immunodeficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 09, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 472 of the ZAP70 protein (p.Arg472Gln). This variant is present in population databases (rs758807149, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with ZAP70-related conditions. ClinVar contains an entry for this variant (Variation ID: 538568). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at