6-157542707-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_024630.3(ZDHHC14):​c.368C>T​(p.Ala123Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZDHHC14
NM_024630.3 missense

Scores

6
6
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.42
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 Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.762

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZDHHC14NM_024630.3 linkc.368C>T p.Ala123Val missense_variant Exon 2 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.368C>T p.Ala123Val missense_variant Exon 2 of 9 1 NM_024630.3 ENSP00000352821.5 Q8IZN3-1
ZDHHC14ENST00000414563.6 linkc.368C>T p.Ala123Val missense_variant Exon 2 of 9 1 ENSP00000410713.2 Q8IZN3-2
ZDHHC14ENST00000518214.5 linkn.122C>T non_coding_transcript_exon_variant Exon 1 of 8 3 ENSP00000428211.1 H0YAX0
ZDHHC14ENST00000523468.5 linkn.119C>T non_coding_transcript_exon_variant Exon 1 of 3 4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461730
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727180
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 02, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.368C>T (p.A123V) alteration is located in exon 2 (coding exon 2) of the ZDHHC14 gene. This alteration results from a C to T substitution at nucleotide position 368, causing the alanine (A) at amino acid position 123 to be replaced by a valine (V). 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
Pathogenic
0.99
BayesDel_addAF
Uncertain
0.073
D
BayesDel_noAF
Benign
-0.13
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.14
.;T
Eigen
Uncertain
0.65
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Benign
0.033
D
MetaRNN
Pathogenic
0.76
D;D
MetaSVM
Benign
-0.79
T
MutationAssessor
Uncertain
2.8
M;M
PrimateAI
Pathogenic
0.87
D
PROVEAN
Uncertain
-3.8
D;D
REVEL
Uncertain
0.32
Sift
Benign
0.063
T;T
Sift4G
Benign
0.078
T;T
Polyphen
0.86
P;D
Vest4
0.80
MutPred
0.35
Loss of disorder (P = 0.0762);Loss of disorder (P = 0.0762);
MVP
0.17
MPC
2.1
ClinPred
0.99
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.31
gMVP
0.84

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-157963739; COSMIC: COSV63075363; API