Variant 7-6585094-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001134389.2(ZDHHC4):c.575G>C(p.Arg192Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000474 in 1,614,094 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00049 ( 0 hom. )

Consequence

ZDHHC4
NM_001134389.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.34

Variant links:

Genes affected

ZDHHC4 (HGNC:18471): (zinc finger DHHC-type palmitoyltransferase 4) Predicted to enable protein-cysteine S-palmitoyltransferase activity. Predicted to be involved in peptidyl-L-cysteine S-palmitoylation and protein targeting to membrane. Located in Golgi apparatus and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ZDHHC4 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC4	NM_001134389.2 linkuse as main transcript	c.575G>C	p.Arg192Thr	missense_variant	7/8	ENST00000335965.11	NP_001127861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC4	ENST00000335965.11 linkuse as main transcript	c.575G>C	p.Arg192Thr	missense_variant	7/8	1	NM_001134389.2	ENSP00000337475	P1
	ENST00000434951.1 linkuse as main transcript	n.280+3601C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000316

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000632

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000290

AC:

AN:

251472

Hom.:

AF XY:

0.000265

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000145

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:

0.000563

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000490

AC:

717

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000458

AC XY:

333

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000612

Gnomad4 OTH exome

AF:

0.000430

GnomAD4 genome

AF:

0.000315

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.000144

Hom.:

Bravo

AF:

0.000321

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000305

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000593

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

Aug 13, 2021

The c.575G>C (p.R192T) alteration is located in exon 7 (coding exon 5) of the ZDHHC4 gene. This alteration results from a G to C substitution at nucleotide position 575, causing the arginine (R) at amino acid position 192 to be replaced by a threonine (T). 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

Uncertain

0.50

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.089

T;T;T;T;T;T

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

.;.;D;.;.;.

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.48

T;T;T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Pathogenic

3.2

M;M;M;M;M;M

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.5

D;D;D;D;D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.024

D;D;D;D;D;D

Sift4G

Benign

0.14

T;T;T;T;T;T

Polyphen

0.98

D;D;D;D;D;D

Vest4

0.63

MVP

0.56

MPC

0.32

ClinPred

0.59

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.28

gMVP

0.88

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