X-129806476-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_016032.4(ZDHHC9):c.989A>G(p.Glu330Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000166 in 1,207,176 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_016032.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZDHHC9 | NM_016032.4 | c.989A>G | p.Glu330Gly | missense_variant | 11/11 | ENST00000357166.11 | |
ZDHHC9 | NM_001008222.3 | c.989A>G | p.Glu330Gly | missense_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZDHHC9 | ENST00000357166.11 | c.989A>G | p.Glu330Gly | missense_variant | 11/11 | 1 | NM_016032.4 | P1 | |
ZDHHC9 | ENST00000371064.7 | c.989A>G | p.Glu330Gly | missense_variant | 10/10 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000897 AC: 1AN: 111471Hom.: 0 Cov.: 23 AF XY: 0.0000297 AC XY: 1AN XY: 33647
GnomAD4 exome AF: 9.13e-7 AC: 1AN: 1095705Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 361079
GnomAD4 genome ? AF: 0.00000897 AC: 1AN: 111471Hom.: 0 Cov.: 23 AF XY: 0.0000297 AC XY: 1AN XY: 33647
ClinVar
Submissions by phenotype
Syndromic X-linked intellectual disability Raymond type Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 14, 2020 | This sequence change replaces glutamic acid with glycine at codon 330 of the ZDHHC9 protein (p.Glu330Gly). The glutamic acid residue is weakly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ZDHHC9-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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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