Variant X-75429984-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_144969.3(ZDHHC15):c.450-4G>A 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 0.0000631 in 1,205,074 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 32 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 0.00013 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.000056 ( 0 hom. 28 hem. )

Consequence

ZDHHC15
NM_144969.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002378

Clinical Significance

Likely benign criteria provided, single submitter B:3

Conservation

PhyloP100: -0.927

Variant links:

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]

ZDHHC15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant X-75429984-C-T is Benign according to our data. Variant chrX-75429984-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 437316.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-75429984-C-T is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC15	NM_144969.3 linkuse as main transcript	c.450-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000373367.8	NP_659406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC15	ENST00000373367.8 linkuse as main transcript	c.450-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_144969.3	ENSP00000362465	P1	Q96MV8-1
ZDHHC15	ENST00000541184.1 linkuse as main transcript	c.423-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2		ENSP00000445420		Q96MV8-3

Frequencies

GnomAD3 genomes

AF:

0.000135

AC:

AN:

111329

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

33543

show subpopulations

Gnomad AFR

AF:

0.0000980

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000283

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000502

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000662

GnomAD3 exomes

AF:

0.000123

AC:

AN:

179243

Hom.:

AF XY:

0.000188

AC XY:

AN XY:

63947

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000297

Gnomad SAS exome

AF:

0.0000548

Gnomad FIN exome

AF:

0.000439

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000558

AC:

AN:

1093695

Hom.:

Cov.:

AF XY:

0.0000779

AC XY:

AN XY:

359361

show subpopulations

Gnomad4 AFR exome

AF:

0.0000381

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000133

Gnomad4 SAS exome

AF:

0.000131

Gnomad4 FIN exome

AF:

0.000222

Gnomad4 NFE exome

AF:

0.0000465

Gnomad4 OTH exome

AF:

0.0000218

GnomAD4 genome

AF:

0.000135

AC:

AN:

111379

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

33603

show subpopulations

Gnomad4 AFR

AF:

0.0000978

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000284

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000502

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000654

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000604

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 05, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.1

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000024

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over