Variant chrX-129814685-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

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. 12/20 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, single submitter B:1

Conservation

PhyloP100: 0.615

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 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_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC9	NM_016032.4 linkuse as main transcript	c.598G>A	p.Ala200Thr	missense_variant	6/11	ENST00000357166.11	NP_057116.2	Q9Y397
ZDHHC9	NM_001008222.3 linkuse as main transcript	c.598G>A	p.Ala200Thr	missense_variant	5/10		NP_001008223.1	Q9Y397
ZDHHC9	XM_047442151.1 linkuse as main transcript	c.598G>A	p.Ala200Thr	missense_variant	6/8		XP_047298107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZDHHC9	ENST00000357166.11 linkuse as main transcript	c.598G>A	p.Ala200Thr	missense_variant	6/11	1	NM_016032.4	ENSP00000349689.6	Q9Y397
ZDHHC9	ENST00000371064.7 linkuse as main transcript	c.598G>A	p.Ala200Thr	missense_variant	5/10	1		ENSP00000360103.3	Q9Y397
ZDHHC9	ENST00000433917.5 linkuse as main transcript	c.365-960G>A		intron_variant		3		ENSP00000406165.1	H0Y6K6

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

111188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33386

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

GnomAD3 exomes

AF:

0.0000327

AC:

AN:

183415

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

67887

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 SAS exome

AF:

0.00

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000662

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000831

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000180

AC:

AN:

111188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33386

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000961

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000282

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Syndromic X-linked intellectual disability Raymond type

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 14, 2023

- -

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

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

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

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