NM_016032.4:c.674+9C>T

Variant names:

• chrX-129813668-G-A
• rs376385410
• NM_016032.4:c.674+9C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The NM_016032.4(ZDHHC9):​c.674+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000787 in 1,207,674 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 23 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., 3 hem., cov: 23)
  • Exomes 𝑓: 0.000074 (0 hom. 20 hem.)
• Consequence: ZDHHC9 NM_016032.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 1.13
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.18).
• BP6: Variant X-129813668-G-A is Benign according to our data. Variant chrX-129813668-G-A is described in ClinVar as Benign. ClinVar VariationId is 537745.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 3 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016032.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC9	NM_016032.4	MANE Select	c.674+9C>T		intron	N/A	NP_057116.2
	ZDHHC9	NM_001008222.3		c.674+9C>T		intron	N/A	NP_001008223.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC9	ENST00000357166.11	TSL:1 MANE Select	c.674+9C>T		intron	N/A	ENSP00000349689.6
	ZDHHC9	ENST00000371064.7	TSL:1	c.674+9C>T		intron	N/A	ENSP00000360103.3
	ZDHHC9	ENST00000433917.5	TSL:3	c.413+9C>T		intron	N/A	ENSP00000406165.1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 14 AN: 112384 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000646

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00111

Gnomad SAS AF: 0.000735

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000113

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000136 AC: 25 AN: 183351 AF XY: 0.000118

Gnomad AFR exome AF: 0.000304

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000289

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000147

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000740 AC: 81 AN: 1095233 Hom.: 0 Cov.: 29 AF XY: 0.0000554 AC XY: 20 AN XY: 360749

African (AFR) AF: 0.0000760 AC: 2 AN: 26330

American (AMR) AF: 0.00 AC: 0 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.0000516 AC: 1 AN: 19369

East Asian (EAS) AF: 0.000232 AC: 7 AN: 30188

South Asian (SAS) AF: 0.000129 AC: 7 AN: 54072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4125

European-Non Finnish (NFE) AF: 0.0000715 AC: 60 AN: 839451

Other (OTH) AF: 0.0000870 AC: 4 AN: 45987

GnomAD4 genome AF: 0.000125 AC: 14 AN: 112441 Hom.: 0 Cov.: 23 AF XY: 0.0000867 AC XY: 3 AN XY: 34609

African (AFR) AF: 0.0000645 AC: 2 AN: 31026

American (AMR) AF: 0.00 AC: 0 AN: 10621

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2657

East Asian (EAS) AF: 0.00111 AC: 4 AN: 3594

South Asian (SAS) AF: 0.000737 AC: 2 AN: 2714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.000113 AC: 6 AN: 53259

Other (OTH) AF: 0.00 AC: 0 AN: 1525

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.000132

EpiCase AF: 0.000218

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Syndromic X-linked intellectual disability Raymond type (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.18
CADD	Benign	14
DANN	Benign	0.80
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs376385410; hg19: chrX-128947644; COSMIC: COSV108880250; COSMIC: COSV108880250;