16-49638805-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001379286.1(ZNF423):c.371C>T(p.Thr124Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000235 in 1,614,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. T124R) has been classified as Uncertain significance.
Frequency
Consequence
NM_001379286.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF423 | NM_001379286.1 | c.371C>T | p.Thr124Met | missense_variant | 4/8 | ENST00000563137.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF423 | ENST00000563137.7 | c.371C>T | p.Thr124Met | missense_variant | 4/8 | 5 | NM_001379286.1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152202Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251098Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135778
GnomAD4 exome AF: 0.0000239 AC: 35AN: 1461764Hom.: 0 Cov.: 35 AF XY: 0.0000316 AC XY: 23AN XY: 727176
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152320Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74478
ClinVar
Submissions by phenotype
Nephronophthisis 14 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 05, 2017 | This sequence change replaces threonine with methionine at codon 116 of the ZNF423 protein (p.Thr116Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs376833288, ExAC 0.01%). This variant has not been reported in the literature in individuals with ZNF423-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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