rs137853201
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP3_Strong
The NM_001079.4(ZAP70):c.1394G>A(p.Arg465His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R465C) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001079.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZAP70 | NM_001079.4 | c.1394G>A | p.Arg465His | missense_variant | 11/14 | ENST00000264972.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZAP70 | ENST00000264972.10 | c.1394G>A | p.Arg465His | missense_variant | 11/14 | 1 | NM_001079.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251240Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135806
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461826Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727218
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Combined immunodeficiency due to ZAP70 deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2001 | - - |
ZAP70-Related Severe Combined Immunodeficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at