NM_178566.6:c.365+1340T>C

Variant names:

• chr9-14660875-A-G
• rs10481504
• NM_178566.6:c.365+1340T>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.365+1340T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,082 control chromosomes in the GnomAD database, including 5,292 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 0.25 (5292 hom., cov: 31)
• Consequence: ZDHHC21 NM_178566.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.769
• Publications: 4 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 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.365+1340T>C		intron	N/A	NP_848661.1	Q8IVQ6
	ZDHHC21	NM_001354118.2		c.365+1340T>C		intron	N/A	NP_001341047.1	Q8IVQ6
	ZDHHC21	NM_001354119.2		c.365+1340T>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.365+1340T>C		intron	N/A	ENSP00000370303.3	Q8IVQ6
	ZDHHC21	ENST00000899578.1		c.365+1340T>C		intron	N/A	ENSP00000569637.1
	ZDHHC21	ENST00000899579.1		c.365+1340T>C		intron	N/A	ENSP00000569638.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38019 AN: 151962 Hom.: 5298 Cov.: 31

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.250 AC: 38008 AN: 152082 Hom.: 5292 Cov.: 31 AF XY: 0.247 AC XY: 18363 AN XY: 74326

African (AFR) AF: 0.136 AC: 5649 AN: 41510

American (AMR) AF: 0.252 AC: 3852 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 956 AN: 3470

East Asian (EAS) AF: 0.350 AC: 1811 AN: 5168

South Asian (SAS) AF: 0.182 AC: 875 AN: 4820

European-Finnish (FIN) AF: 0.252 AC: 2657 AN: 10550

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21414 AN: 67954

Other (OTH) AF: 0.254 AC: 538 AN: 2114

Alfa AF: 0.263 Hom.: 991

Bravo AF: 0.248

Asia WGS AF: 0.216 AC: 751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.74
PhyloP100		0.77
Mutation Taster		=100/0	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: rs10481504; hg19: chr9-14660873; COSMIC: COSV66612746;