rs536601676
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001367624.2(ZNF469):c.9368G>A(p.Arg3123His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000679 in 1,533,972 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R3123C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001367624.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF469 | NM_001367624.2 | c.9368G>A | p.Arg3123His | missense_variant | 3/3 | ENST00000565624.3 | |
ZNF469 | XM_047434810.1 | c.9368G>A | p.Arg3123His | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF469 | ENST00000565624.3 | c.9368G>A | p.Arg3123His | missense_variant | 3/3 | NM_001367624.2 | A2 | ||
ZNF469 | ENST00000437464.1 | c.9284G>A | p.Arg3095His | missense_variant | 2/2 | 5 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00153 AC: 233AN: 152230Hom.: 4 Cov.: 34
GnomAD3 exomes AF: 0.00116 AC: 155AN: 133782Hom.: 3 AF XY: 0.00106 AC XY: 77AN XY: 72968
GnomAD4 exome AF: 0.000585 AC: 808AN: 1381624Hom.: 5 Cov.: 91 AF XY: 0.000573 AC XY: 390AN XY: 681158
GnomAD4 genome AF: 0.00153 AC: 233AN: 152348Hom.: 4 Cov.: 34 AF XY: 0.00234 AC XY: 174AN XY: 74500
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 09, 2017 | The R3095H variant in the ZNF469 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. Adequate data is not available in large population cohorts to assess the frequency of this variant in publicly available databases; however, this variant has not been detected at a significant frequency in presumably healthy individuals tested at GeneDx (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R3095H variant is a conservative amino acid substitution, which occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R3095H as a variant of uncertain significance. - |
Brittle cornea syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 14, 2021 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at