rs199537523

chrX-75478992-TA-TchrX-75478992-TA-TAAchrX-75478992-TA-TAAA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_144969.3(ZDHHC15):c.164-8del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,039,865 control chromosomes in the GnomAD database, including 5 homozygotes. There are 277 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00096 (1 hom., 34 hem., cov: 22)
  • Exomes 𝑓: 0.0024 (4 hom. 243 hem.)
• Consequence: ZDHHC15 NM_144969.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.835

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant X-75478992-TA-T is Benign according to our data. Variant chrX-75478992-TA-T is described in ClinVar as [Benign]. Clinvar id is 212630.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-75478992-TA-T is described in Lovd as [Likely_benign].
• BS2: High Hemizygotes in GnomAd at 34 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC15	NM_144969.3	c.164-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000373367.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC15	ENST00000373367.8	c.164-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_144969.3	P1
ZDHHC15	ENST00000541184.1	c.137-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.000964 AC: 104 AN: 107857 Hom.: 1 Cov.: 22 AF XY: 0.00108 AC XY: 34 AN XY: 31337

Gnomad AFR AF: 0.000335

Gnomad AMI AF: 0.00298

Gnomad AMR AF: 0.000399

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00431

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.00209

GnomAD4 exome AF: 0.00235 AC: 2194 AN: 931971 Hom.: 4 Cov.: 18 AF XY: 0.000898 AC XY: 243 AN XY: 270499

Gnomad4 AFR exome AF: 0.00330

Gnomad4 AMR exome AF: 0.00398

Gnomad4 ASJ exome AF: 0.0289

Gnomad4 EAS exome AF: 0.00132

Gnomad4 SAS exome AF: 0.00127

Gnomad4 FIN exome AF: 0.000751

Gnomad4 NFE exome AF: 0.00181

Gnomad4 OTH exome AF: 0.00310

GnomAD4 genome AF: 0.000964 AC: 104 AN: 107894 Hom.: 1 Cov.: 22 AF XY: 0.00108 AC XY: 34 AN XY: 31386

Gnomad4 AFR AF: 0.000335

Gnomad4 AMR AF: 0.000399

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000367

Gnomad4 OTH AF: 0.00207

Alfa AF: 0.0119 Hom.: 21

Bravo AF: 0.000997

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 10, 2014

- -

Computational scores

Source: dbNSFP v4.3

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: rs199537523; hg19: chrX-74698827;