chr20-45949018-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_022095.4(ZNF335):c.3964G>A(p.Glu1322Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,461,594 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. E1322Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_022095.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF335 | NM_022095.4 | c.3964G>A | p.Glu1322Lys | missense_variant | 28/28 | ENST00000322927.3 | |
ZNF335 | XM_047440363.1 | c.3964G>A | p.Glu1322Lys | missense_variant | 27/27 | ||
ZNF335 | XM_005260504.5 | c.3961G>A | p.Glu1321Lys | missense_variant | 27/27 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF335 | ENST00000322927.3 | c.3964G>A | p.Glu1322Lys | missense_variant | 28/28 | 1 | NM_022095.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250960Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135796
GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461594Hom.: 0 Cov.: 32 AF XY: 0.0000220 AC XY: 16AN XY: 727112
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2022 | 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. 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 disruptive. This variant has not been reported in the literature in individuals affected with ZNF335-related conditions. This variant is present in population databases (rs767339054, gnomAD 0.006%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1322 of the ZNF335 protein (p.Glu1322Lys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at