chr6-157653560-C-T

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

2
16

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]

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
ZDHHC14NM_024630.3 linkc.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
ZDHHC14ENST00000359775.10 linkc.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.:
4
Cov.:
32
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.:
4
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.:
14
Cov.:
31
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.:
4
Cov.:
32
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.:
5
Bravo
AF:
0.00239
TwinsUK
AF:
0.00458
AC:
17
ALSPAC
AF:
0.00182
AC:
7
ESP6500AA
AF:
0.000908
AC:
4
ESP6500EA
AF:
0.00209
AC:
18
ExAC
AF:
0.00272
AC:
330
Asia WGS
AF:
0.00462
AC:
16
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
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0066
.;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-0.94
FATHMM_MKL
Benign
0.69
D
LIST_S2
Uncertain
0.90
D;D
MetaRNN
Benign
0.0046
T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
0.81
L;L
PrimateAI
Benign
0.48
T
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
T
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.

Other links and lift over

dbSNP: rs8180688; hg19: chr6-158074592; COSMIC: COSV100399062; API