NM_032799.5:c.595G>C

Variant names:

• chr9-128721390-C-G
• rs748742304
• NM_032799.5:c.595G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032799.5(ZDHHC12):​c.595G>C​(p.Val199Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V199I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZDHHC12 NM_032799.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.63

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]

ACMG classification

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=0.13122028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC12	NM_032799.5	c.595G>C	p.Val199Leu	missense_variant	Exon 5 of 5	ENST00000372663.9	NP_116188.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZDHHC12	ENST00000372663.9	c.595G>C	p.Val199Leu	missense_variant	Exon 5 of 5	1	NM_032799.5	ENSP00000361748.4
ZDHHC12	ENST00000372667.9	c.637G>C	p.Val213Leu	missense_variant	Exon 5 of 5	5		ENSP00000361752.5
ZDHHC12	ENST00000467312.1	n.2026G>C		non_coding_transcript_exon_variant	Exon 4 of 4	2
ZDHHC12	ENST00000452105.5	c.*7G>C		downstream_gene_variant		2		ENSP00000387587.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0046	T;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.81	N;N
REVEL	Benign	0.099
Sift	Benign	0.33	T;T
Sift4G	Benign	0.65	T;T
Polyphen		0.0030	B;.
Vest4		0.088
MutPred		0.51		Loss of catalytic residue at V199 (P = 0.0762);.;
MVP		0.18
MPC		0.19
ClinPred		0.93	D
GERP RS		4.8
Varity_R		0.16
gMVP		0.57

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

Other links and lift over

dbSNP: rs748742304; hg19: chr9-131483669;