rs769527426

Variant names:

• chrX-129814685-C-A
• rs769527426
• NM_016032.4:c.598G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-129814685-C-A
• chrX-129814685-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016032.4(ZDHHC9):​c.598G>T​(p.Ala200Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A200T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: ZDHHC9 NM_016032.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.615
• Publications: 0 publications found

Genes affected

ZDHHC9 (HGNC:18475): (zinc finger DHHC-type palmitoyltransferase 9) This gene encodes an integral membrane protein that is a member of the zinc finger DHHC domain-containing protein family. The encoded protein forms a complex with golgin subfamily A member 7 and functions as a palmitoyltransferase. This protein specifically palmitoylates HRAS and NRAS. Mutations in this gene are associated with X-linked cognitive disability. Alternate splicing results in multiple transcript variants that encode the same protein.[provided by RefSeq, May 2010]

ZDHHC9 Gene-Disease associations (from GenCC):

• syndromic X-linked intellectual disability Raymond type

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen
• X-linked intellectual disability with marfanoid habitus

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18557116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC9	NM_016032.4	c.598G>T	p.Ala200Ser	missense_variant	Exon 6 of 11	ENST00000357166.11	NP_057116.2
ZDHHC9	NM_001008222.3	c.598G>T	p.Ala200Ser	missense_variant	Exon 5 of 10		NP_001008223.1
ZDHHC9	XM_047442151.1	c.598G>T	p.Ala200Ser	missense_variant	Exon 6 of 8		XP_047298107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZDHHC9	ENST00000357166.11	c.598G>T	p.Ala200Ser	missense_variant	Exon 6 of 11	1	NM_016032.4	ENSP00000349689.6
ZDHHC9	ENST00000371064.7	c.598G>T	p.Ala200Ser	missense_variant	Exon 5 of 10	1		ENSP00000360103.3
ZDHHC9	ENST00000433917.5	c.365-960G>T		intron_variant	Intron 3 of 5	3		ENSP00000406165.1
ZDHHC9	ENST00000406492.2	c.*86G>T		downstream_gene_variant		5		ENSP00000383991.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000545 AC: 1 AN: 183415 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.042	T;T
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.84	.;T
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L
PhyloP100		0.61
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.79	N;N
REVEL	Benign	0.058
Sift	Benign	0.28	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.11	B;B
Vest4		0.33
MutPred		0.60		Loss of catalytic residue at A200 (P = 0.1588);Loss of catalytic residue at A200 (P = 0.1588);
MVP		0.20
MPC		1.0
ClinPred		0.18	T
GERP RS		4.9
Varity_R		0.28
gMVP		0.80
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs769527426; hg19: chrX-128948661;