9-128721783-C-T

Variant names:

• chr9-128721783-C-T
• rs146354591
• NM_032799.5:c.350G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032799.5(ZDHHC12):​c.350G>A​(p.Arg117His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000281 in 1,613,282 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R117C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (1 hom.)
• Consequence: ZDHHC12 NM_032799.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.800
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014626592).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032799.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC12	NM_032799.5	MANE Select	c.350G>A	p.Arg117His	missense	Exon 4 of 5	NP_116188.3
	ZDHHC12	NM_001318015.2		c.515G>A	p.Arg172His	missense	Exon 4 of 5	NP_001304944.2	Q96GR4-3
	ZDHHC12	NM_001318023.2		c.347G>A	p.Arg116His	missense	Exon 4 of 5	NP_001304952.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC12	ENST00000372663.9	TSL:1 MANE Select	c.350G>A	p.Arg117His	missense	Exon 4 of 5	ENSP00000361748.4	Q96GR4-1
	ZDHHC12	ENST00000935787.1		c.512G>A	p.Arg171His	missense	Exon 4 of 5	ENSP00000605846.1
	ZDHHC12	ENST00000372667.9	TSL:5	c.392G>A	p.Arg131His	missense	Exon 4 of 5	ENSP00000361752.5	Q5T269

Frequencies

GnomAD3 genomes AF: 0.000296 AC: 45 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000409 AC: 102 AN: 249418 AF XY: 0.000385

Gnomad AFR exome AF: 0.0000619

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00351

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000446

Gnomad OTH exome AF: 0.000657

GnomAD4 exome AF: 0.000280 AC: 409 AN: 1460964 Hom.: 1 Cov.: 36 AF XY: 0.000296 AC XY: 215 AN XY: 726768

African (AFR) AF: 0.0000896 AC: 3 AN: 33478

American (AMR) AF: 0.000313 AC: 14 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 98 AN: 26102

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52772

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5758

European-Non Finnish (NFE) AF: 0.000231 AC: 257 AN: 1111852

Other (OTH) AF: 0.000398 AC: 24 AN: 60354

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152318 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74472

African (AFR) AF: 0.0000481 AC: 2 AN: 41572

American (AMR) AF: 0.000719 AC: 11 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00289 AC: 10 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68026

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.000661 Hom.: 0

Bravo AF: 0.000416

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000445 AC: 54

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000711

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.028
FATHMM_MKL	Benign	0.45	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.80
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.053
Sift	Benign	0.13	T
Sift4G	Benign	0.14	T
Polyphen		0.11	B
Vest4		0.25
MVP		0.076
MPC		0.22
ClinPred		0.042	T
GERP RS		3.7
Varity_R		0.094
gMVP		0.42
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs146354591; hg19: chr9-131484062;