Variant X-129823718-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5

The ENST00000357166.11(ZDHHC9):c.448C>T(p.Pro150Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,199 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. 13/20 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

ZDHHC9
ENST00000357166.11 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.60

Variant links:

Genes affected

ZDHHC9 (HGNC:18475): (zinc finger DHHC-type palmitoyltransferase 9) This gene encodes an integral membrane protein that is a member of the zinc finger DHHC domain-containing protein family. The encoded protein forms a complex with golgin subfamily A member 7 and functions as a palmitoyltransferase. This protein specifically palmitoylates HRAS and NRAS. Mutations in this gene are associated with X-linked cognitive disability. Alternate splicing results in multiple transcript variants that encode the same protein.[provided by RefSeq, May 2010]

ZDHHC9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

PM1

In a domain DHHC (size 50) in uniprot entity ZDHC9_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in ENST00000357166.11

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.965

PP5

Variant X-129823718-G-A is Pathogenic according to our data. Variant chrX-129823718-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 10712.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZDHHC9	NM_016032.4 linkuse as main transcript	c.448C>T	p.Pro150Ser	missense_variant	5/11	ENST00000357166.11	NP_057116.2
ZDHHC9	NM_001008222.3 linkuse as main transcript	c.448C>T	p.Pro150Ser	missense_variant	4/10		NP_001008223.1
ZDHHC9	XM_047442151.1 linkuse as main transcript	c.448C>T	p.Pro150Ser	missense_variant	5/8		XP_047298107.1
ZDHHC9	XM_011531348.4 linkuse as main transcript	c.448C>T	p.Pro150Ser	missense_variant	5/6		XP_011529650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC9	ENST00000357166.11 linkuse as main transcript	c.448C>T	p.Pro150Ser	missense_variant	5/11	1	NM_016032.4	ENSP00000349689	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1098199

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363553

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Syndromic X-linked intellectual disability Raymond type

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 01, 2007

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.19

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

T;T;T

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.97

.;D;D

M_CAP

Pathogenic

0.85

MetaRNN

Pathogenic

0.96

D;D;D

MetaSVM

Benign

-0.46

MutationAssessor

Pathogenic

3.4

M;M;.

MutationTaster

Benign

1.0

A;A

PrimateAI

Pathogenic

0.88

PROVEAN

Pathogenic

-7.8

D;D;D

REVEL

Pathogenic

0.73

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.0020

D;D;.

Polyphen

1.0

D;D;.

Vest4

0.91

MutPred

0.85

Gain of catalytic residue at P150 (P = 0.0722);Gain of catalytic residue at P150 (P = 0.0722);Gain of catalytic residue at P150 (P = 0.0722);

MVP

0.82

MPC

2.2

ClinPred

1.0

GERP RS

5.7

Varity_R

0.98

gMVP

0.96

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