11-46701093-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The NM_024741.3(ZNF408):c.46C>T(p.Gln16*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_024741.3 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZNF408 | ENST00000311764.3 | c.46C>T | p.Gln16* | stop_gained | Exon 1 of 5 | 1 | NM_024741.3 | ENSP00000309606.2 | ||
ZNF408 | ENST00000526410.1 | n.63C>T | non_coding_transcript_exon_variant | Exon 1 of 3 | 3 | |||||
ZNF408 | ENST00000531866.1 | n.64C>T | non_coding_transcript_exon_variant | Exon 1 of 2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152210Hom.: 0 Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461830Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727214
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152210Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74354
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change creates a premature translational stop signal (p.Gln16*) in the ZNF408 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in ZNF408 cause disease. This variant is present in population databases (no rsID available, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with ZNF408-related conditions. 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