Variant 9-128722488-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032799.5(ZDHHC12):c.187G>A(p.Ala63Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000759 in 1,567,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

ZDHHC12
NM_032799.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40

Variant links:

Genes affected

ZDHHC12 (HGNC:19159): (zinc finger DHHC-type palmitoyltransferase 12) Enables palmitoyltransferase activity. Involved in protein palmitoylation. Located in Golgi apparatus and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ZDHHC12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059451967).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC12	NM_032799.5 link	c.187G>A	p.Ala63Thr	missense_variant	2/5	ENST00000372663.9	NP_116188.3	Q96GR4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC12	ENST00000372663.9 link	c.187G>A	p.Ala63Thr	missense_variant	2/5	1	NM_032799.5	ENSP00000361748.4		Q96GR4-1

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000604

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000551

AC:

AN:

181512

Hom.:

AF XY:

0.0000621

AC XY:

AN XY:

96644

show subpopulations

Gnomad AFR exome

AF:

0.000555

Gnomad AMR exome

AF:

0.0000368

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000397

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000636

AC:

AN:

1415590

Hom.:

Cov.:

AF XY:

0.0000529

AC XY:

AN XY:

700090

show subpopulations

Gnomad4 AFR exome

AF:

0.000524

Gnomad4 AMR exome

AF:

0.0000263

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000187

Gnomad4 SAS exome

AF:

0.0000124

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000533

Gnomad4 OTH exome

AF:

0.000102

GnomAD4 genome

AF:

0.000191

AC:

AN:

151990

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.000604

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.0000966

Hom.:

Bravo

AF:

0.000193

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000418

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 30, 2024

The c.187G>A (p.A63T) alteration is located in exon 2 (coding exon 2) of the ZDHHC12 gene. This alteration results from a G to A substitution at nucleotide position 187, causing the alanine (A) at amino acid position 63 to be replaced by a threonine (T). 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

0.096

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0028

T;T;T;T

Eigen

Benign

-0.022

Eigen_PC

Benign

0.053

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.73

T;T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.059

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;.;.;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.69

N;N;N;N

REVEL

Benign

0.083

Sift

Benign

0.36

T;T;T;T

Sift4G

Benign

0.44

T;T;.;T

Polyphen

0.99

D;.;.;.

Vest4

0.11

MVP

0.10

MPC

0.19

ClinPred

0.019

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.037

gMVP

0.28

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