Variant chrX-75379162-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_144969.3(ZDHHC15):c.1004C>T(p.Thr335Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000819 in 1,209,498 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 25 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.000072 ( 0 hom. 21 hem. )

Consequence

ZDHHC15
NM_144969.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.79

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023301125).

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.1004C>T	p.Thr335Met	missense_variant	11/12	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.1004C>T	p.Thr335Met	missense_variant	11/12	1	NM_144969.3	ENSP00000362465	P1	Q96MV8-1
ZDHHC15	ENST00000541184.1 linkuse as main transcript	c.977C>T	p.Thr326Met	missense_variant	10/11	2		ENSP00000445420		Q96MV8-3

Frequencies

GnomAD3 genomes

AF:

0.000179

AC:

AN:

111822

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33998

show subpopulations

Gnomad AFR

AF:

0.000455

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000375

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000564

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000126

AC:

AN:

183017

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

67545

show subpopulations

Gnomad AFR exome

AF:

0.000608

Gnomad AMR exome

AF:

0.000183

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000722

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000110

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000720

AC:

AN:

1097623

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

363073

show subpopulations

Gnomad4 AFR exome

AF:

0.000720

Gnomad4 AMR exome

AF:

0.000199

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000994

Gnomad4 SAS exome

AF:

0.0000554

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000475

Gnomad4 OTH exome

AF:

0.000109

GnomAD4 genome

AF:

0.000179

AC:

AN:

111875

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34061

show subpopulations

Gnomad4 AFR

AF:

0.000454

Gnomad4 AMR

AF:

0.000190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000377

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000564

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000702

Hom.:

Bravo

AF:

0.000185

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

Ambry Genetics

Feb 27, 2024

The c.1004C>T (p.T335M) alteration is located in exon 11 (coding exon 11) of the ZDHHC15 gene. This alteration results from a C to T substitution at nucleotide position 1004, causing the threonine (T) at amino acid position 335 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.083

T;.

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.0076

MetaRNN

Benign

0.023

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.5

N;.

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

0.26

N;N

REVEL

Benign

0.041

Sift

Benign

0.076

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.0010

B;.

Vest4

0.26

MVP

0.043

MPC

0.39

ClinPred

0.019

GERP RS

2.9

Varity_R

0.024

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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