rs1386478

chr3-113962104-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001320466.2(ZDHHC23):c.*3474A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,446 control chromosomes in the GnomAD database, including 4,900 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 0.23 (4889 hom., cov: 32)
  • Exomes 𝑓: 0.26 (11 hom.)
• Consequence: ZDHHC23 NM_001320466.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.554

Genes affected

ZDHHC23 (HGNC:28654): (zinc finger DHHC-type palmitoyltransferase 23) Predicted to enable protein-cysteine S-palmitoyltransferase activity. Involved in protein localization to plasma membrane and protein palmitoylation. Predicted to be located in Golgi membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC23	NM_001320466.2	c.*3474A>G		3_prime_UTR_variant	5/5	ENST00000638807.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC23	ENST00000638807.2	c.*3474A>G		3_prime_UTR_variant	5/5	5	NM_001320466.2	P1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35073 AN: 151938 Hom.: 4893 Cov.: 32

Gnomad AFR AF: 0.0702

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.271

GnomAD4 exome AF: 0.262 AC: 102 AN: 390 Hom.: 11 Cov.: 0 AF XY: 0.261 AC XY: 60 AN XY: 230

Gnomad4 FIN exome AF: 0.267

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.231 AC: 35069 AN: 152056 Hom.: 4889 Cov.: 32 AF XY: 0.233 AC XY: 17318 AN XY: 74300

Gnomad4 AFR AF: 0.0702

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.270

Alfa AF: 0.273 Hom.: 3326

Bravo AF: 0.224

Asia WGS AF: 0.279 AC: 972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.3
Dann	Benign	0.76

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: rs1386478; hg19: chr3-113680951; COSMIC: COSV55676069; COSMIC: COSV55676069;