Genetic Variant ZDHHC14:p.Thr334Met (chr6-157653560-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_024630.3(ZDHHC14):c.1001C>T(p.Thr334Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,613,990 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0022 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 14 hom. )

Consequence

ZDHHC14
NM_024630.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.94

Variant links:

Genes affected

ZDHHC14 (HGNC:20341): (zinc finger DHHC-type palmitoyltransferase 14) Enables palmitoyltransferase activity. Involved in peptidyl-L-cysteine S-palmitoylation. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ZDHHC14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045975447).

BP6

Variant 6-157653560-C-T is Benign according to our data. Variant chr6-157653560-C-T is described in ClinVar as [Benign]. Clinvar id is 3770533.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC14	NM_024630.3 link	c.1001C>T	p.Thr334Met	missense_variant	Exon 8 of 9	ENST00000359775.10	NP_078906.2	Q8IZN3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZDHHC14	ENST00000359775.10 link	c.1001C>T	p.Thr334Met	missense_variant	Exon 8 of 9	1	NM_024630.3	ENSP00000352821.5		Q8IZN3-1

Frequencies

GnomAD3 genomes

AF:

0.00223

AC:

339

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.0179

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00254

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00281

AC:

706

AN:

251092

Hom.:

AF XY:

0.00263

AC XY:

357

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.000616

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.000795

Gnomad EAS exome

AF:

0.0160

Gnomad SAS exome

AF:

0.000523

Gnomad FIN exome

AF:

0.000326

Gnomad NFE exome

AF:

0.00305

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00321

AC:

4692

AN:

1461678

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

2216

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.000842

Gnomad4 EAS exome

AF:

0.0132

Gnomad4 SAS exome

AF:

0.000672

Gnomad4 FIN exome

AF:

0.000563

Gnomad4 NFE exome

AF:

0.00349

Gnomad4 OTH exome

AF:

0.00230

GnomAD4 genome

AF:

0.00222

AC:

338

AN:

152312

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

163

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.0179

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00254

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00304

Hom.:

Bravo

AF:

0.00239

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.00272

AC:

330

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.00333

EpiControl

AF:

0.00344

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ZDHHC14: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0066

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.90

D;D

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.81

L;L

PrimateAI

Benign

0.48

PROVEAN

Benign

0.17

N;N

REVEL

Benign

0.13

Sift

Benign

0.15

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.052

B;B

Vest4

0.30

MVP

0.068

MPC

0.35

ClinPred

0.011

GERP RS

5.3

Varity_R

0.041

gMVP

0.60

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