2-97732939-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001079.4(ZAP70):c.620C>T(p.Thr207Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000793 in 1,613,992 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T207T) 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.620C>T | p.Thr207Met | missense_variant | 5/14 | ENST00000264972.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZAP70 | ENST00000264972.10 | c.620C>T | p.Thr207Met | missense_variant | 5/14 | 1 | NM_001079.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152246Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251378Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135900
GnomAD4 exome AF: 0.0000848 AC: 124AN: 1461746Hom.: 0 Cov.: 31 AF XY: 0.0000770 AC XY: 56AN XY: 727186
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152246Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74374
ClinVar
Submissions by phenotype
ZAP70-Related Severe Combined Immunodeficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2022 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 207 of the ZAP70 protein (p.Thr207Met). This variant is present in population databases (rs141564129, gnomAD 0.01%). 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: 546868). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 02, 2021 | The c.620C>T (p.T207M) alteration is located in exon 5 (coding exon 3) of the ZAP70 gene. This alteration results from a C to T substitution at nucleotide position 620, causing the threonine (T) at amino acid position 207 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 28, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at