Variant X-75421896-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_144969.3(ZDHHC15):c.831G>C(p.Lys277Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000795 in 1,208,248 control chromosomes in the GnomAD database, including 1 homozygotes. There are 296 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., 15 hem., cov: 21)

Exomes 𝑓: 0.00082 ( 1 hom. 281 hem. )

Consequence

ZDHHC15
NM_144969.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.265

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013935924).

BP6

Variant X-75421896-C-G is Benign according to our data. Variant chrX-75421896-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 252786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-75421896-C-G is described in Lovd as [Benign].

BS2

High Hemizygotes in GnomAd4 at 15 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC15	NM_144969.3 linkuse as main transcript	c.831G>C	p.Lys277Asn	missense_variant	9/12	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.831G>C	p.Lys277Asn	missense_variant	9/12	1	NM_144969.3	ENSP00000362465	P1	Q96MV8-1
ZDHHC15	ENST00000541184.1 linkuse as main transcript	c.804G>C	p.Lys268Asn	missense_variant	8/11	2		ENSP00000445420		Q96MV8-3

Frequencies

GnomAD3 genomes

AF:

0.000504

AC:

AN:

111176

Hom.:

Cov.:

AF XY:

0.000449

AC XY:

AN XY:

33392

show subpopulations

Gnomad AFR

AF:

0.000131

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000193

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:

0.000943

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000444

AC:

AN:

182384

Hom.:

AF XY:

0.000388

AC XY:

AN XY:

66988

show subpopulations

Gnomad AFR exome

AF:

0.000306

Gnomad AMR exome

AF:

0.000221

Gnomad ASJ exome

AF:

0.000402

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000810

Gnomad OTH exome

AF:

0.000446

GnomAD4 exome

AF:

0.000825

AC:

905

AN:

1097072

Hom.:

Cov.:

AF XY:

0.000775

AC XY:

281

AN XY:

362764

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.000228

Gnomad4 ASJ exome

AF:

0.000414

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00101

Gnomad4 OTH exome

AF:

0.000695

GnomAD4 genome

AF:

0.000504

AC:

AN:

111176

Hom.:

Cov.:

AF XY:

0.000449

AC XY:

AN XY:

33392

show subpopulations

Gnomad4 AFR

AF:

0.000131

Gnomad4 AMR

AF:

0.000193

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000943

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000763

Hom.:

Bravo

AF:

0.000484

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00138

AC:

ESP6500AA

AF:

0.00104

AC:

ESP6500EA

AF:

0.00134

AC:

ExAC

AF:

0.000420

AC:

EpiCase

AF:

0.000875

EpiControl

AF:

0.000833

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Aug 24, 2015	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2022	ZDHHC15: BP4, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-1.0

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.068

T;.

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.1

N;.

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

0.55

N;N

REVEL

Benign

0.057

Sift

Benign

0.55

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.0

B;.

Vest4

0.17

MutPred

0.47

Loss of methylation at K277 (P = 0.0064);.;

MVP

0.15

MPC

0.44

ClinPred

0.0064

GERP RS

-1.8

Varity_R

0.074

gMVP

0.34

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