Variant 9-128722556-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000372663.9(ZDHHC12):c.119A>G(p.Glu40Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00051 in 1,592,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00051 ( 0 hom. )

Consequence

ZDHHC12
ENST00000372663.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.06

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:

ZDHHC12 (HGNC:):

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=0.03396246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC12	NM_032799.5 linkuse as main transcript	c.119A>G	p.Glu40Gly	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 linkuse as main transcript	c.119A>G	p.Glu40Gly	missense_variant	2/5	1	NM_032799.5	ENSP00000361748.4		Q96GR4-1

Frequencies

GnomAD3 genomes

AF:

0.000474

AC:

AN:

151970

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000853

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000274

AC:

AN:

215310

Hom.:

AF XY:

0.000285

AC XY:

AN XY:

115766

show subpopulations

Gnomad AFR exome

AF:

0.0000783

Gnomad AMR exome

AF:

0.000129

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000519

Gnomad NFE exome

AF:

0.000539

Gnomad OTH exome

AF:

0.000371

GnomAD4 exome

AF:

0.000514

AC:

741

AN:

1440730

Hom.:

Cov.:

AF XY:

0.000490

AC XY:

350

AN XY:

714450

show subpopulations

Gnomad4 AFR exome

AF:

0.0000604

Gnomad4 AMR exome

AF:

0.000240

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000194

Gnomad4 NFE exome

AF:

0.000634

Gnomad4 OTH exome

AF:

0.000487

GnomAD4 genome

AF:

0.000473

AC:

AN:

152088

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000853

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000579

Hom.:

Bravo

AF:

0.000434

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.000257

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

Jun 30, 2022

The c.119A>G (p.E40G) alteration is located in exon 2 (coding exon 2) of the ZDHHC12 gene. This alteration results from a A to G substitution at nucleotide position 119, causing the glutamic acid (E) at amino acid position 40 to be replaced by a glycine (G). 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

-0.38

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.042

T;T;T;T

Eigen

Benign

-0.0053

Eigen_PC

Benign

0.099

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.89

D;D;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.034

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.;.;.

MutationTaster

Benign

0.97

D;D;D

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.8

D;D;N;N

REVEL

Benign

0.083

Sift

Benign

0.13

T;T;T;D

Sift4G

Benign

0.22

T;T;.;D

Polyphen

0.13

B;.;.;.

Vest4

0.42

MVP

0.38

MPC

0.28

ClinPred

0.036

GERP RS

3.8

Varity_R

0.25

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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