16-88427483-C-T
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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 (★★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
ZNF469
NM_001367624.2 missense
NM_001367624.2 missense
Scores
2
3
13
Clinical Significance
Conservation
PhyloP100: 1.42
Genes affected
ZNF469 (HGNC:23216): (zinc finger protein 469) This gene encodes a zinc-finger protein. Low-percent homology to certain collagens suggests that it may function as a transcription factor or extra-nuclear regulator factor for the synthesis or organization of collagen fibers. Mutations in this gene cause brittle cornea syndrome. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2050708).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZNF469 | NM_001367624.2 | c.13C>T | p.Arg5Cys | missense_variant | 3/3 | ENST00000565624.3 | NP_001354553.1 | |
ZNF469 | XM_047434810.1 | c.13C>T | p.Arg5Cys | missense_variant | 4/4 | XP_047290766.1 | ||
LOC112268182 | XR_007065178.1 | n.251-1217G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZNF469 | ENST00000565624.3 | c.13C>T | p.Arg5Cys | missense_variant | 3/3 | 6 | NM_001367624.2 | ENSP00000456500.2 | ||
ZNF469 | ENST00000437464.1 | c.13C>T | p.Arg5Cys | missense_variant | 1/2 | 5 | ENSP00000402343.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152136Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.00000842 AC: 1AN: 118834Hom.: 0 AF XY: 0.0000154 AC XY: 1AN XY: 64818
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GnomAD4 exome AF: 0.0000103 AC: 14AN: 1363886Hom.: 0 Cov.: 32 AF XY: 0.0000164 AC XY: 11AN XY: 670610
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152136Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1AN XY: 74310
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;.
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Vest4
MutPred
Loss of methylation at R5 (P = 0.0321);Loss of methylation at R5 (P = 0.0321);
MVP
ClinPred
T
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at