Variant rs140526450 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_016032.4(ZDHHC9):c.167+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000414 in 1,209,607 control chromosomes in the GnomAD database, including 1 homozygotes. There are 151 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., 79 hem., cov: 23)

Exomes 𝑓: 0.00022 ( 0 hom. 72 hem. )

Consequence

ZDHHC9
NM_016032.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.128

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 -12 ACMG points.

BP6

Variant X-129841769-C-T is Benign according to our data. Variant chrX-129841769-C-T is described in ClinVar as [Benign]. Clinvar id is 196472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-129841769-C-T is described in Lovd as [Benign].

BS2

High Hemizygotes in GnomAd4 at 79 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ZDHHC9	NM_016032.4 linkuse as main transcript	c.167+10G>A	intron_variant	ENST00000357166.11
ZDHHC9	NM_001008222.3 linkuse as main transcript	c.167+10G>A	intron_variant
ZDHHC9	XM_011531348.4 linkuse as main transcript	c.167+10G>A	intron_variant
ZDHHC9	XM_047442151.1 linkuse as main transcript	c.167+10G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
ZDHHC9	ENST00000357166.11 linkuse as main transcript	c.167+10G>A	intron_variant	1	NM_016032.4	P1
ZDHHC9	ENST00000371064.7 linkuse as main transcript	c.167+10G>A	intron_variant	1		P1
ZDHHC9	ENST00000406492.2 linkuse as main transcript	c.167+10G>A	intron_variant	5
ZDHHC9	ENST00000433917.5 linkuse as main transcript	c.46+10G>A	intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00230

AC:

256

AN:

111486

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

AN XY:

33668

show subpopulations

Gnomad AFR

AF:

0.00806

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000286

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000565

Gnomad OTH

AF:

0.00200

GnomAD3 exomes

AF:

0.000632

AC:

115

AN:

181839

Hom.:

AF XY:

0.000475

AC XY:

AN XY:

67349

show subpopulations

Gnomad AFR exome

AF:

0.00843

Gnomad AMR exome

AF:

0.000109

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000223

AC:

245

AN:

1098069

Hom.:

Cov.:

AF XY:

0.000198

AC XY:

AN XY:

363443

show subpopulations

Gnomad4 AFR exome

AF:

0.00773

Gnomad4 AMR exome

AF:

0.000227

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000202

Gnomad4 OTH exome

AF:

0.000304

GnomAD4 genome

AF:

0.00230

AC:

256

AN:

111538

Hom.:

Cov.:

AF XY:

0.00234

AC XY:

AN XY:

33730

show subpopulations

Gnomad4 AFR

AF:

0.00804

Gnomad4 AMR

AF:

0.000286

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000565

Gnomad4 OTH

AF:

0.00197

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.00263

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jul 21, 2014

- -

ZDHHC9-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 14, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Syndromic X-linked intellectual disability Raymond type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 27, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.5

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.36

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.36

Position offset: 0

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