chr16-49491282-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.3872C>T(p.Ala1291Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,980 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. A1291T) 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.3872C>T | p.Ala1291Val | missense_variant | 8/8 | ENST00000563137.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF423 | ENST00000563137.7 | c.3872C>T | p.Ala1291Val | missense_variant | 8/8 | 5 | NM_001379286.1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251410Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135882
GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461778Hom.: 0 Cov.: 30 AF XY: 0.0000248 AC XY: 18AN XY: 727194
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74344
ClinVar
Submissions by phenotype
Nephronophthisis 14 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 10, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1283 of the ZNF423 protein (p.Ala1283Val). This variant is present in population databases (rs774591168, gnomAD 0.0009%). 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. This variant has not been reported in the literature in individuals affected with ZNF423-related conditions. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at