Variant 1-26851194-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032283.3(ZDHHC18):c.899C>T(p.Thr300Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ZDHHC18
NM_032283.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.55

Variant links:

Genes affected

ZDHHC18 (HGNC:20712): (zinc finger DHHC-type palmitoyltransferase 18) Enables palmitoyltransferase activity. Involved in peptidyl-L-cysteine S-palmitoylation. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ZDHHC18 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	UniProt
ZDHHC18	NM_032283.3 linkuse as main transcript	c.899C>T	p.Thr300Met	missense_variant	6/8	ENST00000374142.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC18	ENST00000374142.9 linkuse as main transcript	c.899C>T	p.Thr300Met	missense_variant	6/8	1	NM_032283.3	P1	Q9NUE0-1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251490

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461860

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000257

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

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

Nov 14, 2023

The c.899C>T (p.T300M) alteration is located in exon 6 (coding exon 6) of the ZDHHC18 gene. This alteration results from a C to T substitution at nucleotide position 899, causing the threonine (T) at amino acid position 300 to be replaced by a methionine (M). 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

0.89

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

0.10

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.18

T;.

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.97

D;D

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.74

D;D

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Pathogenic

-5.5

D;D

REVEL

Uncertain

0.50

Sift

Benign

0.034

D;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

1.0

D;.

Vest4

0.94

MVP

0.26

MPC

1.6

ClinPred

0.98

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.39

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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