20-41202083-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001384317.1(ZHX3):c.2834C>G(p.Ser945Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000218 in 1,606,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001384317.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZHX3 | NM_001384317.1 | c.2834C>G | p.Ser945Trp | missense_variant | Exon 3 of 4 | ENST00000683867.1 | NP_001371246.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152110Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000975 AC: 24AN: 246206Hom.: 0 AF XY: 0.000105 AC XY: 14AN XY: 132890
GnomAD4 exome AF: 0.0000227 AC: 33AN: 1454686Hom.: 0 Cov.: 31 AF XY: 0.0000249 AC XY: 18AN XY: 722642
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152110Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74296
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.2834C>G (p.S945W) alteration is located in exon 3 (coding exon 1) of the ZHX3 gene. This alteration results from a C to G substitution at nucleotide position 2834, causing the serine (S) at amino acid position 945 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces serine, which is neutral and polar, with tryptophan, which is neutral and slightly polar, at codon 945 of the ZHX3 protein (p.Ser945Trp). This variant is present in population databases (rs762813790, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ZHX3-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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