Genetic Variant NM_016032.4:c.626-10A>T (chrX-129813735-T-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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

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 -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 VariationId 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	Exon rank	MANE	Protein	UniProt
ZDHHC9	NM_016032.4 link	c.626-10A>T	intron_variant	Intron 6 of 10	ENST00000357166.11	NP_057116.2	Q9Y397
ZDHHC9	NM_001008222.3 link	c.626-10A>T	intron_variant	Intron 5 of 9		NP_001008223.1	Q9Y397
ZDHHC9	XM_047442151.1 link	c.626-10A>T	intron_variant	Intron 6 of 7		XP_047298107.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZDHHC9	ENST00000357166.11 link	c.626-10A>T	intron_variant	Intron 6 of 10	1	NM_016032.4	ENSP00000349689.6	Q9Y397
ZDHHC9	ENST00000371064.7 link	c.626-10A>T	intron_variant	Intron 5 of 9	1		ENSP00000360103.3	Q9Y397
ZDHHC9	ENST00000433917.5 link	c.365-10A>T	intron_variant	Intron 3 of 5	3		ENSP00000406165.1	H0Y6K6

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

113

AN:

112087

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00142

AC:

260

AN:

182723

AF XY:

0.00131

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 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

African (AFR)

AF:

0.0000380

AC:

AN:

26301

American (AMR)

AF:

0.00

AC:

AN:

35191

Ashkenazi Jewish (ASJ)

AF:

0.0000517

AC:

AN:

19351

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30177

South Asian (SAS)

AF:

0.0000556

AC:

AN:

53981

European-Finnish (FIN)

AF:

0.0115

AC:

464

AN:

40443

Middle Eastern (MID)

AF:

0.000243

AC:

AN:

4118

European-Non Finnish (NFE)

AF:

0.000288

AC:

241

AN:

837218

Other (OTH)

AF:

0.000915

AC:

AN:

45907

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

112

140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00101

AC:

113

AN:

112141

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

AN XY:

34323

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30927

American (AMR)

AF:

0.00

AC:

AN:

10586

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.000561

AC:

AN:

3562

South Asian (SAS)

AF:

0.00

AC:

AN:

2708

European-Finnish (FIN)

AF:

0.0133

AC:

AN:

6099

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.000564

AC:

AN:

53182

Other (OTH)

AF:

0.00

AC:

AN:

1521

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Nov 11, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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