NM_022095.4:c.3912T>A
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4
The NM_022095.4(ZNF335):c.3912T>A(p.Asp1304Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_022095.4 missense
Scores
Clinical Significance
Conservation
Publications
- microcephalic primordial dwarfism due to ZNF335 deficiencyInheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
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ACMG classification
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZNF335 | NM_022095.4 | c.3912T>A | p.Asp1304Glu | missense_variant | Exon 28 of 28 | ENST00000322927.3 | NP_071378.1 | |
ZNF335 | XM_047440363.1 | c.3912T>A | p.Asp1304Glu | missense_variant | Exon 27 of 27 | XP_047296319.1 | ||
ZNF335 | XM_005260504.5 | c.3909T>A | p.Asp1303Glu | missense_variant | Exon 27 of 27 | XP_005260561.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 1304 of the ZNF335 protein (p.Asp1304Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ZNF335-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 disruptive. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at