X-75421980-G-A

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.747C>T(p.Cys249=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000874 in 1,206,364 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 343 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., 10 hem., cov: 22)
  • Exomes 𝑓: 0.00092 (0 hom. 333 hem.)
• Consequence: ZDHHC15 NM_144969.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.106

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=-0.52).
• BP6: Variant X-75421980-G-A is Benign according to our data. Variant chrX-75421980-G-A is described in ClinVar as [Benign]. Clinvar id is 199186.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.106 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC15	NM_144969.3	c.747C>T	p.Cys249=	synonymous_variant	9/12	ENST00000373367.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC15	ENST00000373367.8	c.747C>T	p.Cys249=	synonymous_variant	9/12	1	NM_144969.3	P1
ZDHHC15	ENST00000541184.1	c.720C>T	p.Cys240=	synonymous_variant	8/11	2

Frequencies

GnomAD3 genomes AF: 0.000439 AC: 49 AN: 111733 Hom.: 0 Cov.: 22 AF XY: 0.000295 AC XY: 10 AN XY: 33915

Gnomad AFR AF: 0.000293

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000752

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000537 AC: 96 AN: 178820 Hom.: 0 AF XY: 0.000581 AC XY: 37 AN XY: 63654

Gnomad AFR exome AF: 0.000312

Gnomad AMR exome AF: 0.000113

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000879

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000885

Gnomad OTH exome AF: 0.000459

GnomAD4 exome AF: 0.000918 AC: 1005 AN: 1094631 Hom.: 0 Cov.: 30 AF XY: 0.000924 AC XY: 333 AN XY: 360539

Gnomad4 AFR exome AF: 0.0000763

Gnomad4 AMR exome AF: 0.0000862

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000749

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00108

Gnomad4 OTH exome AF: 0.00107

GnomAD4 genome AF: 0.000439 AC: 49 AN: 111733 Hom.: 0 Cov.: 22 AF XY: 0.000295 AC XY: 10 AN XY: 33915

Gnomad4 AFR AF: 0.000293

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000752

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000391 Hom.: 2

Bravo AF: 0.000521

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 05, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 06, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	8.1
Dann	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs147278537; hg19: chrX-74641815;