Variant chrX-129813735-T-A 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.626-10A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00072 in 1,204,828 control chromosomes in the GnomAD database, including 1 homozygotes. There are 288 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., 63 hem., cov: 23)

Exomes 𝑓: 0.00069 ( 1 hom. 225 hem. )

Consequence

ZDHHC9
NM_016032.4 intron

Scores

Splicing: ADA: 0.08731

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.699

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant X-129813735-T-A is Benign according to our data. Variant chrX-129813735-T-A is described in ClinVar as [Benign]. Clinvar id is 537744.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 63 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ZDHHC9	NM_016032.4 linkuse as main transcript	c.626-10A>T	intron_variant	ENST00000357166.11	NP_057116.2	Q9Y397
ZDHHC9	NM_001008222.3 linkuse as main transcript	c.626-10A>T	intron_variant		NP_001008223.1	Q9Y397
ZDHHC9	XM_047442151.1 linkuse as main transcript	c.626-10A>T	intron_variant		XP_047298107.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ZDHHC9	ENST00000357166.11 linkuse as main transcript	c.626-10A>T	intron_variant	1	NM_016032.4	ENSP00000349689.6	Q9Y397
ZDHHC9	ENST00000371064.7 linkuse as main transcript	c.626-10A>T	intron_variant	1		ENSP00000360103.3	Q9Y397
ZDHHC9	ENST00000433917.5 linkuse as main transcript	c.365-10A>T	intron_variant	3		ENSP00000406165.1	H0Y6K6

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

113

AN:

112087

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

AN XY:

34259

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:

0.000560

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0133

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000564

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00142

AC:

260

AN:

182723

Hom.:

AF XY:

0.00131

AC XY:

AN XY:

67195

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0112

Gnomad NFE exome

AF:

0.000883

Gnomad OTH exome

AF:

0.00243

GnomAD4 exome

AF:

0.000690

AC:

754

AN:

1092687

Hom.:

Cov.:

AF XY:

0.000628

AC XY:

225

AN XY:

358167

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000517

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000556

Gnomad4 FIN exome

AF:

0.0115

Gnomad4 NFE exome

AF:

0.000288

Gnomad4 OTH exome

AF:

0.000915

GnomAD4 genome

AF:

0.00101

AC:

113

AN:

112141

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

AN XY:

34323

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000561

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0133

Gnomad4 NFE

AF:

0.000564

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000763

Hom.:

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

Dec 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.087

dbscSNV1_RF

Benign

0.29

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