X-129814685-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_016032.4(ZDHHC9):c.598G>A(p.Ala200Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,209,050 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000010 ( 0 hom. 3 hem. )

Consequence

ZDHHC9
NM_016032.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

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: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12991226).

BP6

Variant X-129814685-C-T is Benign according to our data. Variant chrX-129814685-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 573424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAdExome4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC9	NM_016032.4 link	c.598G>A	p.Ala200Thr	missense_variant	Exon 6 of 11	ENST00000357166.11	NP_057116.2	Q9Y397
ZDHHC9	NM_001008222.3 link	c.598G>A	p.Ala200Thr	missense_variant	Exon 5 of 10		NP_001008223.1	Q9Y397
ZDHHC9	XM_047442151.1 link	c.598G>A	p.Ala200Thr	missense_variant	Exon 6 of 8		XP_047298107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZDHHC9	ENST00000357166.11 link	c.598G>A	p.Ala200Thr	missense_variant	Exon 6 of 11	1	NM_016032.4	ENSP00000349689.6	Q9Y397
ZDHHC9	ENST00000371064.7 link	c.598G>A	p.Ala200Thr	missense_variant	Exon 5 of 10	1		ENSP00000360103.3	Q9Y397
ZDHHC9	ENST00000433917.5 link	c.365-960G>A		intron_variant	Intron 3 of 5	3		ENSP00000406165.1	H0Y6K6
ZDHHC9	ENST00000406492.2 link	c.*86G>A		downstream_gene_variant		5		ENSP00000383991.2	Q5JYE8

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

111188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000961

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000282

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000327

AC:

AN:

183415

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000361

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000100

AC:

AN:

1097862

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

363236

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26388

American (AMR)

AF:

0.0000284

AC:

AN:

35198

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19377

East Asian (EAS)

AF:

0.0000662

AC:

AN:

30193

South Asian (SAS)

AF:

0.00

AC:

AN:

54133

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40500

Middle Eastern (MID)

AF:

0.000245

AC:

AN:

4076

European-Non Finnish (NFE)

AF:

0.00000831

AC:

AN:

841941

Other (OTH)

AF:

0.00

AC:

AN:

46056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000180

AC:

AN:

111188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33386

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30562

American (AMR)

AF:

0.0000961

AC:

AN:

10411

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2642

East Asian (EAS)

AF:

0.000282

AC:

AN:

3549

South Asian (SAS)

AF:

0.00

AC:

AN:

2647

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5918

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53072

Other (OTH)

AF:

0.00

AC:

AN:

1469

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

May 02, 2025

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Syndromic X-linked intellectual disability Raymond type

Benign:1

Jan 19, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.064

T;T

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.85

.;D

M_CAP

Benign

0.041

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L

PhyloP100

0.61

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.085

Sift

Benign

0.078

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.25

B;B

Vest4

0.30

MutPred

0.57

Loss of stability (P = 0.0912);Loss of stability (P = 0.0912);

MVP

0.19

MPC

1.1

ClinPred

0.11

GERP RS

4.9

Varity_R

0.31

gMVP

0.82

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

X-129814685-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over