Variant X-75429100-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_144969.3(ZDHHC15):c.581G>A(p.Ser194Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000406 in 1,206,266 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., 5 hem., cov: 23)

Exomes 𝑓: 0.000024 ( 0 hom. 5 hem. )

Consequence

ZDHHC15
NM_144969.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 3.15

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:

ZDHHC15 (HGNC:):

ZDHHC15 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028299004).

BP6

Variant X-75429100-C-T is Benign according to our data. Variant chrX-75429100-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2378041.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Hemizygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC15	NM_144969.3 linkuse as main transcript	c.581G>A	p.Ser194Asn	missense_variant	7/12	ENST00000373367.8	NP_659406.1	Q96MV8-1B3KY34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC15	ENST00000373367.8 linkuse as main transcript	c.581G>A	p.Ser194Asn	missense_variant	7/12	1	NM_144969.3	ENSP00000362465.3		Q96MV8-1
ZDHHC15	ENST00000541184.1 linkuse as main transcript	c.554G>A	p.Ser185Asn	missense_variant	6/11	2		ENSP00000445420.1		Q96MV8-3

Frequencies

GnomAD3 genomes

AF:

0.000216

AC:

AN:

111295

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

33523

show subpopulations

Gnomad AFR

AF:

0.000751

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:

0.00

Gnomad OTH

AF:

0.000666

GnomAD3 exomes

AF:

0.0000620

AC:

AN:

177555

Hom.:

AF XY:

0.0000481

AC XY:

AN XY:

62423

show subpopulations

Gnomad AFR exome

AF:

0.000852

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000237

AC:

AN:

1094918

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

360792

show subpopulations

Gnomad4 AFR exome

AF:

0.000839

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.0000653

GnomAD4 genome

AF:

0.000207

AC:

AN:

111348

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

33586

show subpopulations

Gnomad4 AFR

AF:

0.000717

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000658

Alfa

AF:

0.0000171

Hom.:

Bravo

AF:

0.000276

ESP6500AA

AF:

0.00156

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2022

The c.581G>A (p.S194N) alteration is located in exon 7 (coding exon 7) of the ZDHHC15 gene. This alteration results from a G to A substitution at nucleotide position 581, causing the serine (S) at amino acid position 194 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

ZDHHC15: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.092

T;.

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.028

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.78

N;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.090

N;N

REVEL

Benign

0.059

Sift

Benign

0.039

D;D

Sift4G

Benign

0.24

T;T

Polyphen

0.0010

B;.

Vest4

0.19

MVP

0.082

MPC

0.36

ClinPred

0.062

GERP RS

1.9

Varity_R

0.11

gMVP

0.59

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