rs751918374

Variant names:

• chrX-129812718-G-A
• rs751918374
• NM_016032.4:c.777C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-129812718-G-A
• chrX-129812718-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4 BP6_Moderate BP7 BS2

The NM_016032.4(ZDHHC9):​c.777C>T​(p.Asp259Asp) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,198,491 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 0.000028 (0 hom. 5 hem.)
• Consequence: ZDHHC9 NM_016032.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.0005012
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.38
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.219).
• BP6: Variant X-129812718-G-A is Benign according to our data. Variant chrX-129812718-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 470202.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.38 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 2 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.777C>T	p.Asp259Asp	splice_region synonymous	Exon 8 of 11	NP_057116.2
	ZDHHC9	NM_001008222.3		c.777C>T	p.Asp259Asp	splice_region synonymous	Exon 7 of 10	NP_001008223.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC9	ENST00000357166.11	TSL:1 MANE Select	c.777C>T	p.Asp259Asp	splice_region synonymous	Exon 8 of 11	ENSP00000349689.6
	ZDHHC9	ENST00000371064.7	TSL:1	c.777C>T	p.Asp259Asp	splice_region synonymous	Exon 7 of 10	ENSP00000360103.3
	ZDHHC9	ENST00000433917.5	TSL:3	c.516C>T	p.Asp172Asp	splice_region synonymous	Exon 5 of 6	ENSP00000406165.1

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 112017 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000949

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000600 AC: 11 AN: 183204 AF XY: 0.0000296

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000328

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000721

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000276 AC: 30 AN: 1086474 Hom.: 0 Cov.: 29 AF XY: 0.0000142 AC XY: 5 AN XY: 353122

African (AFR) AF: 0.0000382 AC: 1 AN: 26163

American (AMR) AF: 0.000284 AC: 10 AN: 35195

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19323

East Asian (EAS) AF: 0.0000664 AC: 2 AN: 30141

South Asian (SAS) AF: 0.00 AC: 0 AN: 53885

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4107

European-Non Finnish (NFE) AF: 0.0000180 AC: 15 AN: 831547

Other (OTH) AF: 0.0000438 AC: 2 AN: 45709

GnomAD4 genome AF: 0.0000179 AC: 2 AN: 112017 Hom.: 0 Cov.: 23 AF XY: 0.0000585 AC XY: 2 AN XY: 34177

African (AFR) AF: 0.00 AC: 0 AN: 30811

American (AMR) AF: 0.0000949 AC: 1 AN: 10542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3551

South Asian (SAS) AF: 0.00 AC: 0 AN: 2726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53196

Other (OTH) AF: 0.00 AC: 0 AN: 1513

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Syndromic X-linked intellectual disability Raymond type (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.035
DANN	Benign	0.59
PhyloP100		-2.4
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00050
dbscSNV1_RF	Benign	0.014
SpliceAI score (max)		0.010		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: rs751918374; hg19: chrX-128946694;