dbSNP rs769527426: ZDHHC9:p.Ala200Ser (chrX-129814685-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000357166.11(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
ENST00000357166.11 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.615

Publications

0 publications found

Variant links:

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

ZDHHC9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000357166.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC9	NM_016032.4	MANE Select	c.598G>T	p.Ala200Ser	missense	Exon 6 of 11	NP_057116.2
	ZDHHC9	NM_001008222.3		c.598G>T	p.Ala200Ser	missense	Exon 5 of 10	NP_001008223.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ZDHHC9	ENST00000357166.11	TSL:1 MANE Select	c.598G>T	p.Ala200Ser	missense	Exon 6 of 11	ENSP00000349689.6
ZDHHC9	ENST00000371064.7	TSL:1	c.598G>T	p.Ala200Ser	missense	Exon 5 of 10	ENSP00000360103.3
ZDHHC9	ENST00000433917.5	TSL:3	c.365-960G>T		intron	N/A	ENSP00000406165.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000545

AC:

AN:

183415

AF XY:

0.00

show subpopulations

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.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.042

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.84

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

0.61

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.79

REVEL

Benign

0.058

Sift

Benign

0.28

Sift4G

Benign

0.27

Polyphen

0.11

Vest4

0.33

MutPred

0.60

Loss of catalytic residue at A200 (P = 0.1588)

MVP

0.20

MPC

1.0

ClinPred

0.18

GERP RS

4.9

Varity_R

0.28

gMVP

0.80

Mutation Taster

=82/18

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over