1-26856493-T-G

Variant summary

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

The NM_032283.3(ZDHHC18):c.*2650T>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 0.724 in 235,672 control chromosomes in the GnomAD database, including 63,484 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 0.71 (39654 hom., cov: 31)
  • Exomes 𝑓: 0.74 (23830 hom.)
• Consequence: ZDHHC18 NM_032283.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.53

Genes affected

ZDHHC18 (HGNC:20712): (zinc finger DHHC-type palmitoyltransferase 18) Enables palmitoyltransferase activity. Involved in peptidyl-L-cysteine S-palmitoylation. Located in Golgi apparatus. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC18	NM_032283.3	c.*2650T>G		3_prime_UTR_variant	8/8	ENST00000374142.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC18	ENST00000374142.9	c.*2650T>G		3_prime_UTR_variant	8/8	1	NM_032283.3	P1
ZDHHC18	ENST00000488397.3	c.*36+231T>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108404 AN: 151912 Hom.: 39607 Cov.: 31

Gnomad AFR AF: 0.814

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.867

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.717

GnomAD4 exome AF: 0.744 AC: 62199 AN: 83642 Hom.: 23830 Cov.: 0 AF XY: 0.757 AC XY: 35893 AN XY: 47402

Gnomad4 AFR exome AF: 0.840

Gnomad4 AMR exome AF: 0.802

Gnomad4 ASJ exome AF: 0.708

Gnomad4 EAS exome AF: 0.998

Gnomad4 SAS exome AF: 0.862

Gnomad4 FIN exome AF: 0.647

Gnomad4 NFE exome AF: 0.642

Gnomad4 OTH exome AF: 0.723

GnomAD4 genome AF: 0.714 AC: 108506 AN: 152030 Hom.: 39654 Cov.: 31 AF XY: 0.719 AC XY: 53443 AN XY: 74306

Gnomad4 AFR AF: 0.815

Gnomad4 AMR AF: 0.762

Gnomad4 ASJ AF: 0.675

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.866

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.722

Alfa AF: 0.643 Hom.: 50238

Bravo AF: 0.728

Asia WGS AF: 0.927 AC: 3225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.011
Dann	Benign	0.38

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: rs10902646; hg19: chr1-27182984;