X-129806265-G-A

Position:

• chrX-129806265-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000357166.11(ZDHHC9):​c.*105C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 736,488 control chromosomes in the GnomAD database, including 845 homozygotes. There are 3,016 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (510 hom., 1803 hem., cov: 23)
  • Exomes 𝑓: 0.0080 (335 hom. 1213 hem.)
• Consequence: ZDHHC9 ENST00000357166.11 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.294

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant X-129806265-G-A is Benign according to our data. Variant chrX-129806265-G-A is described in ClinVar as [Benign]. Clinvar id is 1285857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC9	NM_016032.4	c.*105C>T		3_prime_UTR_variant	11/11	ENST00000357166.11	NP_057116.2
ZDHHC9	NM_001008222.3	c.*105C>T		3_prime_UTR_variant	10/10		NP_001008223.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC9	ENST00000357166.11	c.*105C>T		3_prime_UTR_variant	11/11	1	NM_016032.4	ENSP00000349689	P1
ZDHHC9	ENST00000371064.7	c.*105C>T		3_prime_UTR_variant	10/10	1		ENSP00000360103	P1

Frequencies

GnomAD3 genomes AF: 0.0601 AC: 6735 AN: 112038 Hom.: 510 Cov.: 23 AF XY: 0.0523 AC XY: 1788 AN XY: 34218

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0262

Gnomad ASJ AF: 0.00227

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00109

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000863

Gnomad OTH AF: 0.0542

GnomAD4 exome AF: 0.00805 AC: 5025 AN: 624393 Hom.: 335 Cov.: 10 AF XY: 0.00639 AC XY: 1213 AN XY: 189809

Gnomad4 AFR exome AF: 0.219

Gnomad4 AMR exome AF: 0.0132

Gnomad4 ASJ exome AF: 0.00300

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000534

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000468

Gnomad4 OTH exome AF: 0.0168

GnomAD4 genome AF: 0.0602 AC: 6750 AN: 112095 Hom.: 510 Cov.: 23 AF XY: 0.0526 AC XY: 1803 AN XY: 34285

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.0262

Gnomad4 ASJ AF: 0.00227

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000729

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000864

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0138 Hom.: 379

Bravo AF: 0.0723

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.0
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs1053440; hg19: chrX-128940241;