9-14687869-A-G

Position:

• chr9-14687869-A-G

Variant summary

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

The NM_178566.6(ZDHHC21):​c.-176+2468T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 150,452 control chromosomes in the GnomAD database, including 14,887 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 0.43 (14887 hom., cov: 32)
• Consequence: ZDHHC21 NM_178566.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

Genes affected

ZDHHC21 (HGNC:20750): (zinc finger DHHC-type palmitoyltransferase 21) Enables palmitoyltransferase activity. Involved in peptidyl-L-cysteine S-palmitoylation. Located in Golgi apparatus and plasma membrane. [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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC21	NM_178566.6	c.-176+2468T>C		intron_variant		ENST00000380916.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC21	ENST00000380916.9	c.-176+2468T>C		intron_variant		1	NM_178566.6	P1
ZDHHC21	ENST00000497966.1	n.86+2468T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64282 AN: 150338 Hom.: 14855 Cov.: 32

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.414

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.428 AC: 64368 AN: 150452 Hom.: 14887 Cov.: 32 AF XY: 0.429 AC XY: 31538 AN XY: 73570

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.420

Alfa AF: 0.422 Hom.: 1770

Bravo AF: 0.427

Asia WGS AF: 0.389 AC: 1350 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7865184; hg19: chr9-14687867;