16-88427483-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001367624.2(ZNF469):c.13C>T(p.Arg5Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,516,022 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. R5H) has been classified as Likely benign.
Frequency
Consequence
NM_001367624.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF469 | NM_001367624.2 | c.13C>T | p.Arg5Cys | missense_variant | 3/3 | ENST00000565624.3 | |
LOC112268182 | XR_007065178.1 | n.251-1217G>A | intron_variant, non_coding_transcript_variant | ||||
ZNF469 | XM_047434810.1 | c.13C>T | p.Arg5Cys | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF469 | ENST00000565624.3 | c.13C>T | p.Arg5Cys | missense_variant | 3/3 | NM_001367624.2 | A2 | ||
ZNF469 | ENST00000437464.1 | c.13C>T | p.Arg5Cys | missense_variant | 1/2 | 5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152136Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000842 AC: 1AN: 118834Hom.: 0 AF XY: 0.0000154 AC XY: 1AN XY: 64818
GnomAD4 exome AF: 0.0000103 AC: 14AN: 1363886Hom.: 0 Cov.: 32 AF XY: 0.0000164 AC XY: 11AN XY: 670610
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152136Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1AN XY: 74310
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 5 of the ZNF469 protein (p.Arg5Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with ZNF469-related conditions. 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: "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. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 22, 2024 | The p.R5C variant (also known as c.13C>T), located in coding exon 1 of the ZNF469 gene, results from a C to T substitution at nucleotide position 13. The arginine at codon 5 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at