Variant 13-21400374-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001330059.2(ZDHHC20):c.593C>T(p.Thr198Met) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000241 in 1,579,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

ZDHHC20
NM_001330059.2 missense, splice_region

Scores

Splicing: ADA: 0.5461

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.44

Variant links:

Genes affected

ZDHHC20 (HGNC:20749): (zinc finger DHHC-type palmitoyltransferase 20) Enables protein-cysteine S-palmitoyltransferase activity and zinc ion binding activity. Involved in peptidyl-L-cysteine S-palmitoylation. Located in intracellular membrane-bounded organelle and plasma membrane. Is integral component of Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

ZDHHC20 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35520217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC20	NM_001330059.2 linkuse as main transcript	c.593C>T	p.Thr198Met	missense_variant, splice_region_variant	7/13	ENST00000400590.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC20	ENST00000400590.8 linkuse as main transcript	c.593C>T	p.Thr198Met	missense_variant, splice_region_variant	7/13	5	NM_001330059.2	P1	Q5W0Z9-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151848

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000366

AC:

AN:

218816

Hom.:

AF XY:

0.0000252

AC XY:

AN XY:

119270

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000128

Gnomad SAS exome

AF:

0.000125

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000287

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000252

AC:

AN:

1427582

Hom.:

Cov.:

AF XY:

0.0000240

AC XY:

AN XY:

708932

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000308

Gnomad4 SAS exome

AF:

0.0000647

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000163

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151848

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74134

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000166

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

May 18, 2023

The c.593C>T (p.T198M) alteration is located in exon 7 (coding exon 7) of the ZDHHC20 gene. This alteration results from a C to T substitution at nucleotide position 593, causing the threonine (T) at amino acid position 198 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

Benign

0.15

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.14

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.94

D;D;.;D;D

M_CAP

Benign

0.059

MetaRNN

Benign

0.36

T;T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.8

L;.;L;L;L

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-4.7

D;D;D;D;D

REVEL

Benign

0.25

Sift

Uncertain

0.0090

D;D;D;D;D

Sift4G

Benign

0.084

T;T;T;T;T

Polyphen

0.76

P;D;.;.;.

Vest4

0.52

MutPred

0.43

.;Loss of ubiquitination at K132 (P = 0.1166);.;.;.;

MVP

0.16

MPC

1.6

ClinPred

0.52

GERP RS

4.9

Varity_R

0.32

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.55

dbscSNV1_RF

Benign

0.51

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