Genetic Variant ZDHHC15:p.Val162Val (chrX-75429195-A-G) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP7BS2

The NM_144969.3(ZDHHC15):c.486T>C(p.Val162Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,194,437 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V162V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000018 ( 0 hom. 8 hem. )

Consequence

ZDHHC15
NM_144969.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.73

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

intellectual disability, X-linked 91
Inheritance: XL, Unknown Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
X-linked complex neurodevelopmental disorder
Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

ZDHHC15 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP7

Synonymous conserved (PhyloP=1.73 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 8 XL,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC15	NM_144969.3 link	c.486T>C	p.Val162Val	synonymous_variant	Exon 7 of 12	ENST00000373367.8	NP_659406.1	Q96MV8-1B3KY34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZDHHC15	ENST00000373367.8 link	c.486T>C	p.Val162Val	synonymous_variant	Exon 7 of 12	1	NM_144969.3	ENSP00000362465.3		Q96MV8-1
ZDHHC15	ENST00000541184.1 link	c.459T>C	p.Val153Val	synonymous_variant	Exon 6 of 11	2		ENSP00000445420.1		Q96MV8-3

Frequencies

GnomAD3 genomes

AF:

0.00000896

AC:

AN:

111558

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000303

AC:

AN:

165028

AF XY:

0.0000365

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000655

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000175

AC:

AN:

1082879

Hom.:

Cov.:

AF XY:

0.0000226

AC XY:

AN XY:

353433

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25188

American (AMR)

AF:

0.00

AC:

AN:

30878

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18698

East Asian (EAS)

AF:

0.00

AC:

AN:

29894

South Asian (SAS)

AF:

0.00

AC:

AN:

51089

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40300

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3956

European-Non Finnish (NFE)

AF:

0.0000215

AC:

AN:

837518

Other (OTH)

AF:

0.0000220

AC:

AN:

45358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000896

AC:

AN:

111558

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33714

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30735

American (AMR)

AF:

0.00

AC:

AN:

10406

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2642

East Asian (EAS)

AF:

0.00

AC:

AN:

3544

South Asian (SAS)

AF:

0.00

AC:

AN:

2633

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6079

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53097

Other (OTH)

AF:

0.00

AC:

AN:

1503

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

8.8

(source)

DANN

Benign

0.79

PhyloP100

1.7

Mutation Taster

=98/2

polymorphism

(source)

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

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X-75429195-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over