Variant 22-20141525-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_013373.4(ZDHHC8):c.1120G>A(p.Glu374Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZDHHC8
NM_013373.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.05

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.42016435).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZDHHC8	NM_013373.4 linkuse as main transcript	c.1120G>A	p.Glu374Lys	missense_variant	9/11	ENST00000334554.12	NP_037505.1
ZDHHC8	NM_001185024.2 linkuse as main transcript	c.1120G>A	p.Glu374Lys	missense_variant	9/11		NP_001171953.1
ZDHHC8	XM_006724239.3 linkuse as main transcript	c.1120G>A	p.Glu374Lys	missense_variant	9/12		XP_006724302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC8	ENST00000334554.12 linkuse as main transcript	c.1120G>A	p.Glu374Lys	missense_variant	9/11	1	NM_013373.4	ENSP00000334490	P4	Q9ULC8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458758

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725490

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 15, 2021

The c.1120G>A (p.E374K) alteration is located in exon 9 (coding exon 9) of the ZDHHC8 gene. This alteration results from a G to A substitution at nucleotide position 1120, causing the glutamic acid (E) at amino acid position 374 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.037

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.15

T;.;.

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.42

T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.9

L;.;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.26

N;N;N

REVEL

Benign

0.14

Sift

Benign

0.65

T;T;T

Sift4G

Benign

0.56

T;T;T

Polyphen

0.92

P;P;D

Vest4

0.53

MVP

0.32

MPC

0.30

ClinPred

0.93

GERP RS

5.1

Varity_R

0.16

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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