rs144128364

chrX-75379158-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_144969.3(ZDHHC15):c.1008A>G(p.Glu336=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0006 in 1,209,708 control chromosomes in the GnomAD database, including 1 homozygotes. There are 229 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., 6 hem., cov: 23)
  • Exomes 𝑓: 0.00064 (1 hom. 223 hem.)
• Consequence: ZDHHC15 NM_144969.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.20

Genes affected

ZDHHC15 (HGNC:20342): (zinc finger DHHC-type palmitoyltransferase 15) The protein encoded by this gene belongs to the DHHC palmitoyltransferase family. Mutations in this gene are associated with mental retardatio X-linked type 91 (MRX91). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant X-75379158-T-C is Benign according to our data. Variant chrX-75379158-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 212628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.2 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC15	NM_144969.3	c.1008A>G	p.Glu336=	synonymous_variant	11/12	ENST00000373367.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC15	ENST00000373367.8	c.1008A>G	p.Glu336=	synonymous_variant	11/12	1	NM_144969.3	P1
ZDHHC15	ENST00000541184.1	c.981A>G	p.Glu327=	synonymous_variant	10/11	2

Frequencies

GnomAD3 genomes AF: 0.000259 AC: 29 AN: 112039 Hom.: 0 Cov.: 23 AF XY: 0.000175 AC XY: 6 AN XY: 34191

Gnomad AFR AF: 0.0000649

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000380

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00426

Gnomad NFE AF: 0.000413

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000262 AC: 48 AN: 183018 Hom.: 0 AF XY: 0.000311 AC XY: 21 AN XY: 67552

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000329

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000453

Gnomad OTH exome AF: 0.000443

GnomAD4 exome AF: 0.000635 AC: 697 AN: 1097616 Hom.: 1 Cov.: 30 AF XY: 0.000614 AC XY: 223 AN XY: 363070

Gnomad4 AFR exome AF: 0.0000379

Gnomad4 AMR exome AF: 0.000256

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000247

Gnomad4 NFE exome AF: 0.000791

Gnomad4 OTH exome AF: 0.000434

GnomAD4 genome AF: 0.000259 AC: 29 AN: 112092 Hom.: 0 Cov.: 23 AF XY: 0.000175 AC XY: 6 AN XY: 34254

Gnomad4 AFR AF: 0.0000647

Gnomad4 AMR AF: 0.000379

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000413

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000564 Hom.: 5

Bravo AF: 0.000321

EpiCase AF: 0.000382

EpiControl AF: 0.000653

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 18, 2017

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

ZDHHC15: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	6.8
Dann	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs144128364; hg19: chrX-74598993;