X-75421896-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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

Publications

2 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 -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.

BS2

High Hemizygotes in GnomAd4 at 15 XL,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC15	NM_144969.3 link	c.831G>C	p.Lys277Asn	missense_variant	Exon 9 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.831G>C	p.Lys277Asn	missense_variant	Exon 9 of 12	1	NM_144969.3	ENSP00000362465.3		Q96MV8-1
ZDHHC15	ENST00000541184.1 link	c.804G>C	p.Lys268Asn	missense_variant	Exon 8 of 11	2		ENSP00000445420.1		Q96MV8-3

Frequencies

GnomAD3 genomes

AF:

0.000504

AC:

AN:

111176

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000444

AC:

AN:

182384

AF XY:

0.000388

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 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

African (AFR)

AF:

0.000114

AC:

AN:

26340

American (AMR)

AF:

0.000228

AC:

AN:

35081

Ashkenazi Jewish (ASJ)

AF:

0.000414

AC:

AN:

19328

East Asian (EAS)

AF:

0.00

AC:

AN:

30174

South Asian (SAS)

AF:

0.00

AC:

AN:

54038

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40508

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4124

European-Non Finnish (NFE)

AF:

0.00101

AC:

854

AN:

841436

Other (OTH)

AF:

0.000695

AC:

AN:

46043

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

126

157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000504

AC:

AN:

111176

Hom.:

Cov.:

AF XY:

0.000449

AC XY:

AN XY:

33392

show subpopulations

African (AFR)

AF:

0.000131

AC:

AN:

30574

American (AMR)

AF:

0.000193

AC:

AN:

10355

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2643

East Asian (EAS)

AF:

0.00

AC:

AN:

3522

South Asian (SAS)

AF:

0.00

AC:

AN:

2614

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6042

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.000943

AC:

AN:

53018

Other (OTH)

AF:

0.00

AC:

AN:

1484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Aug 24, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ZDHHC15: BP4, BS2 -

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

(source)

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;.

PhyloP100

-0.27

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

Mutation Taster

=87/13

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

X-75421896-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over