Variant chr22-20140879-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_013373.4(ZDHHC8):c.761T>C(p.Val254Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,601,876 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0017 ( 6 hom. )

Consequence

ZDHHC8
NM_013373.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.107

Variant links:

Genes affected

ZDHHC8 (HGNC:18474): (zinc finger DHHC-type palmitoyltransferase 8) This gene encodes a four transmembrane protein that is a member of the zinc finger DHHC domain-containing protein family. The encoded protein may function as a palmitoyltransferase. Defects in this gene may be associated with a susceptibility to schizophrenia. Alternate splicing of this gene results in multiple transcript variants. A pseudogene of this gene is found on chromosome 22.[provided by RefSeq, May 2010]

ZDHHC8 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=0.006756246).

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC8	NM_013373.4 link	c.761T>C	p.Val254Ala	missense_variant	7/11	ENST00000334554.12	NP_037505.1	Q9ULC8-1
ZDHHC8	NM_001185024.2 link	c.761T>C	p.Val254Ala	missense_variant	7/11		NP_001171953.1	Q9ULC8-3
ZDHHC8	XM_006724239.3 link	c.761T>C	p.Val254Ala	missense_variant	7/12		XP_006724302.1	Q9ULC8-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC8	ENST00000334554.12 link	c.761T>C	p.Val254Ala	missense_variant	7/11	1	NM_013373.4	ENSP00000334490.7		Q9ULC8-1

Frequencies

GnomAD3 genomes

AF:

0.00117

AC:

178

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00212

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00111

AC:

263

AN:

237944

Hom.:

AF XY:

0.00116

AC XY:

152

AN XY:

130536

show subpopulations

Gnomad AFR exome

AF:

0.000258

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000375

Gnomad NFE exome

AF:

0.00205

Gnomad OTH exome

AF:

0.00117

GnomAD4 exome

AF:

0.00169

AC:

2456

AN:

1449604

Hom.:

Cov.:

AF XY:

0.00162

AC XY:

1172

AN XY:

721558

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.00111

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.000647

Gnomad4 NFE exome

AF:

0.00201

Gnomad4 OTH exome

AF:

0.00217

GnomAD4 genome

AF:

0.00116

AC:

177

AN:

152272

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00210

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00182

Hom.:

Bravo

AF:

0.00108

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.00111

AC:

134

EpiCase

AF:

0.00202

EpiControl

AF:

0.00184

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Feb 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.060

T;.;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.49

T;T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.0068

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.2

N;.;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

1.1

N;N;N

REVEL

Benign

0.080

Sift

Benign

0.72

T;T;T

Sift4G

Benign

0.41

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.16

MVP

0.093

MPC

1.2

ClinPred

0.0019

GERP RS

0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.084

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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