Variant X-75478992-TA-TAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_144969.3(ZDHHC15):c.164-8_164-7insT 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 0.00688 in 1,038,903 control chromosomes in the GnomAD database, including 21 homozygotes. There are 1,108 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0045 ( 0 hom., 145 hem., cov: 22)

Exomes 𝑓: 0.0072 ( 21 hom. 963 hem. )

Consequence

ZDHHC15
NM_144969.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.835

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00447 (482/107905) while in subpopulation SAS AF= 0.0337 (85/2521). AF 95% confidence interval is 0.0279. There are 0 homozygotes in gnomad4. There are 145 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Hemizygotes in GnomAd4 at 145 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC15	NM_144969.3 linkuse as main transcript	c.164-8_164-7insT		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 linkuse as main transcript	c.164-8_164-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_144969.3	P1	Q96MV8-1
ZDHHC15	ENST00000541184.1 linkuse as main transcript	c.137-8_137-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2			Q96MV8-3

Frequencies

GnomAD3 genomes

AF:

0.00447

AC:

482

AN:

107869

Hom.:

Cov.:

AF XY:

0.00459

AC XY:

144

AN XY:

31349

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00279

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0101

Gnomad SAS

AF:

0.0336

Gnomad FIN

AF:

0.00485

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00501

Gnomad OTH

AF:

0.00209

GnomAD4 exome

AF:

0.00716

AC:

6670

AN:

930998

Hom.:

Cov.:

AF XY:

0.00357

AC XY:

963

AN XY:

269700

show subpopulations

Gnomad4 AFR exome

AF:

0.00413

Gnomad4 AMR exome

AF:

0.00469

Gnomad4 ASJ exome

AF:

0.00173

Gnomad4 EAS exome

AF:

0.00895

Gnomad4 SAS exome

AF:

0.0278

Gnomad4 FIN exome

AF:

0.00442

Gnomad4 NFE exome

AF:

0.00635

Gnomad4 OTH exome

AF:

0.00734

GnomAD4 genome

AF:

0.00447

AC:

482

AN:

107905

Hom.:

Cov.:

AF XY:

0.00462

AC XY:

145

AN XY:

31397

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00279

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0101

Gnomad4 SAS

AF:

0.0337

Gnomad4 FIN

AF:

0.00485

Gnomad4 NFE

AF:

0.00501

Gnomad4 OTH

AF:

0.00206

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 14, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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