Variant chr9-128721390-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032799.5(ZDHHC12):c.595G>A(p.Val199Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,429,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

ZDHHC12
NM_032799.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.63

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.091892004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC12	NM_032799.5 link	c.595G>A	p.Val199Ile	missense_variant	5/5	ENST00000372663.9	NP_116188.3	Q96GR4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZDHHC12	ENST00000372663.9 link	c.595G>A	p.Val199Ile	missense_variant	5/5	1	NM_032799.5	ENSP00000361748.4	Q96GR4-1
ZDHHC12	ENST00000372667.9 link	c.637G>A	p.Val213Ile	missense_variant	5/5	5		ENSP00000361752.5	Q5T269
ZDHHC12	ENST00000467312.1 link	n.2026G>A		non_coding_transcript_exon_variant	4/4	2
ZDHHC12	ENST00000452105.5 link	c.*7G>A		downstream_gene_variant		2		ENSP00000387587.1	Q5T266

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000308

AC:

AN:

194754

Hom.:

AF XY:

0.0000288

AC XY:

AN XY:

104192

show subpopulations

Gnomad AFR exome

AF:

0.000169

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000680

Gnomad SAS exome

AF:

0.0000781

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000197

GnomAD4 exome

AF:

0.0000112

AC:

AN:

1429454

Hom.:

Cov.:

AF XY:

0.00000989

AC XY:

AN XY:

707950

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.0000261

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000260

Gnomad4 SAS exome

AF:

0.0000365

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000730

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000249

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

Jul 02, 2024

The c.595G>A (p.V199I) alteration is located in exon 5 (coding exon 5) of the ZDHHC12 gene. This alteration results from a G to A substitution at nucleotide position 595, causing the valine (V) at amino acid position 199 to be replaced by an isoleucine (I). 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

0.095

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0025

T;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.092

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.55

N;N

REVEL

Benign

0.10

Sift

Benign

0.20

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.030

B;.

Vest4

0.063

MutPred

0.45

Gain of sheet (P = 0.0221);.;

MVP

0.10

MPC

0.15

ClinPred

0.16

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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