9-128721401-C-G

Variant names:

• chr9-128721401-C-G
• rs1446039659
• NM_032799.5:c.584G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032799.5(ZDHHC12):​c.584G>C​(p.Ser195Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 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: 7.0e-7 (0 hom.)
• Consequence: ZDHHC12 NM_032799.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04433009).

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.584G>C	p.Ser195Thr	missense	Exon 5 of 5	NP_116188.3
	ZDHHC12	NM_001318015.2		c.749G>C	p.Ser250Thr	missense	Exon 5 of 5	NP_001304944.2	Q96GR4-3
	ZDHHC12	NM_001318023.2		c.581G>C	p.Ser194Thr	missense	Exon 5 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.584G>C	p.Ser195Thr	missense	Exon 5 of 5	ENSP00000361748.4	Q96GR4-1
	ZDHHC12	ENST00000935787.1		c.746G>C	p.Ser249Thr	missense	Exon 5 of 5	ENSP00000605846.1
	ZDHHC12	ENST00000372667.9	TSL:5	c.626G>C	p.Ser209Thr	missense	Exon 5 of 5	ENSP00000361752.5	Q5T269

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000519 AC: 1 AN: 192806 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000120

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428578 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 707368

African (AFR) AF: 0.00 AC: 0 AN: 33050

American (AMR) AF: 0.00 AC: 0 AN: 37978

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25408

East Asian (EAS) AF: 0.00 AC: 0 AN: 38456

South Asian (SAS) AF: 0.00 AC: 0 AN: 82086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1095544

Other (OTH) AF: 0.00 AC: 0 AN: 59260

GnomAD4 genome Cov.: 32

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	0.072
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Benign	0.63
DEOGEN2	Benign	0.0058	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.3
PROVEAN	Benign	2.5	N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D
MutPred		0.25		Loss of solvent accessibility (P = 0.0238)
MVP		0.12
ClinPred		0.036	T
GERP RS		-0.049
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.063
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs1446039659; hg19: chr9-131483680;