chr12-76822501-G-A

Position:

• chr12-76822501-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015336.4(ZDHHC17):​c.867G>A​(p.Pro289Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,606,792 control chromosomes in the GnomAD database, including 28,261 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1960 hom., cov: 31)
  • Exomes 𝑓: 0.18 (26301 hom.)
• Consequence: ZDHHC17 NM_015336.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336

Genes affected

ZDHHC17 (HGNC:18412): (zinc finger DHHC-type palmitoyltransferase 17) Enables identical protein binding activity and protein-cysteine S-palmitoyltransferase activity. Involved in lipoprotein transport and protein palmitoylation. Located in Golgi membrane; Golgi-associated vesicle membrane; and aggresome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=-0.336 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC17	NM_015336.4	c.867G>A	p.Pro289Pro	synonymous_variant	8/17	ENST00000426126.7	NP_056151.2
ZDHHC17	NM_001359626.1	c.837G>A	p.Pro279Pro	synonymous_variant	8/17		NP_001346555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC17	ENST00000426126.7	c.867G>A	p.Pro289Pro	synonymous_variant	8/17	1	NM_015336.4	ENSP00000403397.2

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21751 AN: 151358 Hom.: 1960 Cov.: 31

Gnomad AFR AF: 0.0652

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0184

Gnomad SAS AF: 0.0948

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.0865

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.135

GnomAD3 exomes AF: 0.148 AC: 35490 AN: 239094 Hom.: 3178 AF XY: 0.151 AC XY: 19570 AN XY: 129552

Gnomad AFR exome AF: 0.0640

Gnomad AMR exome AF: 0.0739

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.0171

Gnomad SAS exome AF: 0.103

Gnomad FIN exome AF: 0.237

Gnomad NFE exome AF: 0.199

Gnomad OTH exome AF: 0.156

GnomAD4 exome AF: 0.183 AC: 265810 AN: 1455334 Hom.: 26301 Cov.: 33 AF XY: 0.181 AC XY: 131141 AN XY: 723516

Gnomad4 AFR exome AF: 0.0644

Gnomad4 AMR exome AF: 0.0789

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.0195

Gnomad4 SAS exome AF: 0.0991

Gnomad4 FIN exome AF: 0.237

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.163

GnomAD4 genome AF: 0.144 AC: 21750 AN: 151458 Hom.: 1960 Cov.: 31 AF XY: 0.143 AC XY: 10551 AN XY: 73930

Gnomad4 AFR AF: 0.0651

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.0181

Gnomad4 SAS AF: 0.0949

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.135

Alfa AF: 0.181 Hom.: 5330

Bravo AF: 0.132

Asia WGS AF: 0.0790 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.2
DANN	Benign	0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs17813975; hg19: chr12-77216281; COSMIC: COSV58354241; COSMIC: COSV58354241;