chr16-88427484-GC-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001367624.2(ZNF469):c.19del(p.Arg7GlufsTer8) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000732 in 1,365,990 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. R5R) 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.19del | p.Arg7GlufsTer8 | frameshift_variant | 3/3 | ENST00000565624.3 | |
LOC112268182 | XR_007065178.1 | n.251-1219del | intron_variant, non_coding_transcript_variant | ||||
ZNF469 | XM_047434810.1 | c.19del | p.Arg7GlufsTer8 | frameshift_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF469 | ENST00000565624.3 | c.19del | p.Arg7GlufsTer8 | frameshift_variant | 3/3 | NM_001367624.2 | A2 | ||
ZNF469 | ENST00000437464.1 | c.19del | p.Arg7GlufsTer8 | frameshift_variant | 1/2 | 5 | P4 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD4 exome AF: 7.32e-7 AC: 1AN: 1365990Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 671890
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 21, 2023 | This sequence change creates a premature translational stop signal (p.Arg7Glufs*8) 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