Variant X-129806432-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_016032.4(ZDHHC9):c.1033G>A(p.Glu345Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000364 in 1,209,930 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 20 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E345A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000081 ( 0 hom., 4 hem., cov: 22)

Exomes 𝑓: 0.000032 ( 0 hom. 16 hem. )

Consequence

ZDHHC9
NM_016032.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.60

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0057949126).

BP6

Variant X-129806432-C-T is Benign according to our data. Variant chrX-129806432-C-T is described in ClinVar as [Benign]. Clinvar id is 737510.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC9	NM_016032.4 linkuse as main transcript	c.1033G>A	p.Glu345Lys	missense_variant	11/11	ENST00000357166.11
ZDHHC9	NM_001008222.3 linkuse as main transcript	c.1033G>A	p.Glu345Lys	missense_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC9	ENST00000357166.11 linkuse as main transcript	c.1033G>A	p.Glu345Lys	missense_variant	11/11	1	NM_016032.4	P1
ZDHHC9	ENST00000371064.7 linkuse as main transcript	c.1033G>A	p.Glu345Lys	missense_variant	10/10	1		P1

Frequencies

GnomAD3 genomes

AF:

0.0000806

AC:

AN:

111680

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33836

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00252

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

GnomAD3 exomes

AF:

0.000191

AC:

AN:

183448

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

67886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00209

Gnomad SAS exome

AF:

0.000315

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000319

AC:

AN:

1098195

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

363549

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000596

Gnomad4 SAS exome

AF:

0.000259

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000237

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000805

AC:

AN:

111735

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33901

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00253

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000982

ExAC

AF:

0.000296

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Syndromic X-linked intellectual disability Raymond type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 15, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.020

T;T

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.80

.;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.0058

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;N

MutationTaster

Benign

0.51

D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.050

N;N

REVEL

Benign

0.060

Sift

Benign

0.51

T;T

Sift4G

Benign

0.64

T;T

Polyphen

0.0010

B;B

Vest4

0.12

MutPred

0.26

Gain of methylation at E345 (P = 5e-04);Gain of methylation at E345 (P = 5e-04);

MVP

0.21

MPC

1.2

ClinPred

0.055

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.26

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over