rs753460205
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_022095.4(ZNF335):c.2744_2747del(p.Ser915ThrfsTer3) variant causes a frameshift change. The variant allele was found at a frequency of 0.000131 in 1,613,832 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. S915S) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_022095.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF335 | NM_022095.4 | c.2744_2747del | p.Ser915ThrfsTer3 | frameshift_variant | 19/28 | ENST00000322927.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF335 | ENST00000322927.3 | c.2744_2747del | p.Ser915ThrfsTer3 | frameshift_variant | 19/28 | 1 | NM_022095.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152150Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000121 AC: 30AN: 248128Hom.: 0 AF XY: 0.000119 AC XY: 16AN XY: 134330
GnomAD4 exome AF: 0.000128 AC: 187AN: 1461564Hom.: 0 AF XY: 0.000136 AC XY: 99AN XY: 727050
GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152268Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74450
ClinVar
Submissions by phenotype
Microcephalic primordial dwarfism due to ZNF335 deficiency Pathogenic:5
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 01, 2017 | This frameshift variant is categorized as deleterious according to ACMG guidelines (PMID:18414213) and was found twice in our laboratory: in trans with an inframe deletion (V242del) in a 3-year-old female with idiopathic pulmonary arterial hypertension, significant delays, hypotonia, microcephaly, dysmorphisms, broad thumbs and halluxes, hirsutism. A similarly affected microcephalic sister was also compound heterozygous. Also found in trans with a nonsense variant (E1263X) in an 8-year-old male with microcephaly, intellectual disability, seizures, hypomyelination, partial cytochrome c oxidase deficiency. - |
Likely pathogenic, criteria provided, single submitter | research | Duke University Health System Sequencing Clinic, Duke University Health System | Apr 20, 2023 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 17, 2020 | - - |
Pathogenic, no assertion criteria provided | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | - | This variant was identified as compound heterozygous in an individual with developmental delay, intellectual disability, seizures, hypomyelination, and failure to thrive. - |
Pathogenic, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 26, 2024 | - - |
not provided Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes | Jul 06, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at