12-76822501-G-A

Variant names:

• chr12-76822501-G-A
• rs17813975
• NM_015336.4:c.867G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015336.4. 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
	ZDHHC17	NM_015336.4	MANE Select	c.867G>A	p.Pro289Pro	synonymous	Exon 8 of 17	NP_056151.2
	ZDHHC17	NM_001359626.1		c.837G>A	p.Pro279Pro	synonymous	Exon 8 of 17	NP_001346555.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC17	ENST00000426126.7	TSL:1 MANE Select	c.867G>A	p.Pro289Pro	synonymous	Exon 8 of 17	ENSP00000403397.2
	ZDHHC17	ENST00000968885.1		c.966G>A	p.Pro322Pro	synonymous	Exon 9 of 18	ENSP00000638944.1
	ZDHHC17	ENST00000550876.1	TSL:4	c.378G>A	p.Pro126Pro	synonymous	Exon 5 of 6	ENSP00000449734.1

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

GnomAD2 exomes AF: 0.148 AC: 35490 AN: 239094 AF XY: 0.151

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 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

African (AFR) AF: 0.0644 AC: 2148 AN: 33330

American (AMR) AF: 0.0789 AC: 3454 AN: 43752

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 3608 AN: 25994

East Asian (EAS) AF: 0.0195 AC: 770 AN: 39572

South Asian (SAS) AF: 0.0991 AC: 8466 AN: 85436

European-Finnish (FIN) AF: 0.237 AC: 12610 AN: 53192

Middle Eastern (MID) AF: 0.0990 AC: 569 AN: 5750

European-Non Finnish (NFE) AF: 0.202 AC: 224356 AN: 1108140

Other (OTH) AF: 0.163 AC: 9829 AN: 60168

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

African (AFR) AF: 0.0651 AC: 2693 AN: 41336

American (AMR) AF: 0.106 AC: 1603 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 464 AN: 3470

East Asian (EAS) AF: 0.0181 AC: 93 AN: 5146

South Asian (SAS) AF: 0.0949 AC: 455 AN: 4796

European-Finnish (FIN) AF: 0.231 AC: 2388 AN: 10334

Middle Eastern (MID) AF: 0.0862 AC: 25 AN: 290

European-Non Finnish (NFE) AF: 0.201 AC: 13631 AN: 67892

Other (OTH) AF: 0.135 AC: 283 AN: 2096

Alfa AF: 0.176 Hom.: 10735

Bravo AF: 0.132

Asia WGS AF: 0.0790 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.2
DANN	Benign	0.46
PhyloP100		-0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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