9-14687869-A-G

Variant names:

• chr9-14687869-A-G
• rs7865184
• NM_178566.6:c.-176+2468T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178566.6. 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
	ZDHHC21	NM_178566.6	MANE Select	c.-176+2468T>C		intron	N/A	NP_848661.1	Q8IVQ6
	ZDHHC21	NM_001354118.2		c.-351+378T>C		intron	N/A	NP_001341047.1	Q8IVQ6
	ZDHHC21	NM_001354119.2		c.-339+2468T>C		intron	N/A	NP_001341048.1	Q8IVQ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC21	ENST00000380916.9	TSL:1 MANE Select	c.-176+2468T>C		intron	N/A	ENSP00000370303.3	Q8IVQ6
	ZDHHC21	ENST00000899584.1		c.-198T>C		5_prime_UTR_premature_start_codon_gain	Exon 3 of 11	ENSP00000569643.1
	ZDHHC21	ENST00000899584.1		c.-198T>C		5_prime_UTR	Exon 3 of 11	ENSP00000569643.1

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

African (AFR) AF: 0.491 AC: 19571 AN: 39882

American (AMR) AF: 0.372 AC: 5674 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1394 AN: 3468

East Asian (EAS) AF: 0.248 AC: 1287 AN: 5188

South Asian (SAS) AF: 0.400 AC: 1929 AN: 4820

European-Finnish (FIN) AF: 0.482 AC: 5080 AN: 10550

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27799 AN: 67978

Other (OTH) AF: 0.420 AC: 885 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.84
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7865184; hg19: chr9-14687867;