rs188156112

chrX-129813735-T-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_016032.4(ZDHHC9):c.626-10A>T variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.08731
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.699

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]

ACMG classification

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 GnomAd at 63 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC9	NM_016032.4	c.626-10A>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000357166.11
ZDHHC9	NM_001008222.3	c.626-10A>T		splice_polypyrimidine_tract_variant, intron_variant
ZDHHC9	XM_047442151.1	c.626-10A>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC9	ENST00000357166.11	c.626-10A>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_016032.4	P1
ZDHHC9	ENST00000371064.7	c.626-10A>T		splice_polypyrimidine_tract_variant, intron_variant		1		P1
ZDHHC9	ENST00000433917.5	c.367-10A>T		splice_polypyrimidine_tract_variant, intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00101 AC: 113 AN: 112087 Hom.: 0 Cov.: 23 AF XY: 0.00184 AC XY: 63 AN XY: 34259

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.: 0 AF XY: 0.00131 AC XY: 88 AN XY: 67195

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.: 1 Cov.: 28 AF XY: 0.000628 AC XY: 225 AN XY: 358167

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.: 0 Cov.: 23 AF XY: 0.00184 AC XY: 63 AN XY: 34323

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.: 6

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Syndromic X-linked intellectual disability Raymond type Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	16
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

Other links and lift over

dbSNP: rs188156112; hg19: chrX-128947711;