chr16-88427500-G-GC
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001367624.2(ZNF469):c.36dup(p.Thr13HisfsTer137) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000916 in 1,528,596 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. P10P) has been classified as Likely benign.
Frequency
Consequence
NM_001367624.2 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF469 | NM_001367624.2 | c.36dup | p.Thr13HisfsTer137 | frameshift_variant | 3/3 | ENST00000565624.3 | |
LOC112268182 | XR_007065178.1 | n.251-1235_251-1234insG | intron_variant, non_coding_transcript_variant | ||||
ZNF469 | XM_047434810.1 | c.36dup | p.Thr13HisfsTer137 | frameshift_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF469 | ENST00000565624.3 | c.36dup | p.Thr13HisfsTer137 | frameshift_variant | 3/3 | NM_001367624.2 | A2 | ||
ZNF469 | ENST00000437464.1 | c.36dup | p.Thr13HisfsTer137 | frameshift_variant | 1/2 | 5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152084Hom.: 0 Cov.: 34
GnomAD4 exome AF: 0.00000944 AC: 13AN: 1376512Hom.: 0 Cov.: 32 AF XY: 0.0000103 AC XY: 7AN XY: 678356
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152084Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74300
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2024 | This sequence change creates a premature translational stop signal (p.Thr13Hisfs*137) in the ZNF469 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ZNF469 are known to be pathogenic (PMID: 23642083, 23680354). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ZNF469-related conditions. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at