chr2-97734544-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001079.4(ZAP70):c.914C>T(p.Pro305Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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. P305S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001079.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZAP70 | NM_001079.4 | c.914C>T | p.Pro305Leu | missense_variant | 9/14 | ENST00000264972.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZAP70 | ENST00000264972.10 | c.914C>T | p.Pro305Leu | missense_variant | 9/14 | 1 | NM_001079.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152244Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 251026Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135700
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461668Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727144
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152244Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74372
ClinVar
Submissions by phenotype
ZAP70-Related Severe Combined Immunodeficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 19, 2020 | This variant is present in population databases (rs762428344, ExAC 0.002%). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ZAP70-related disease. This sequence change replaces proline with leucine at codon 305 of the ZAP70 protein (p.Pro305Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 28, 2023 | The c.914C>T (p.P305L) alteration is located in exon 9 (coding exon 7) of the ZAP70 gene. This alteration results from a C to T substitution at nucleotide position 914, causing the proline (P) at amino acid position 305 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at