chr9-14662262-A-G

Variant names:

• chr9-14662262-A-G
• rs17215796
• NM_178566.6:c.318T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_178566.6(ZDHHC21):​c.318T>C​(p.Cys106Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,611,824 control chromosomes in the GnomAD database, including 17,552 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 0.12 (1305 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16247 hom.)
• Consequence: ZDHHC21 NM_178566.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• Publications: 15 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=1.54 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC21	NM_178566.6	c.318T>C	p.Cys106Cys	synonymous_variant	Exon 6 of 10	ENST00000380916.9	NP_848661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZDHHC21	ENST00000380916.9	c.318T>C	p.Cys106Cys	synonymous_variant	Exon 6 of 10	1	NM_178566.6	ENSP00000370303.3

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17928 AN: 152158 Hom.: 1307 Cov.: 32

Gnomad AFR AF: 0.0470

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.0168

Gnomad SAS AF: 0.0496

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.144

GnomAD2 exomes AF: 0.126 AC: 31544 AN: 250046 AF XY: 0.124

Gnomad AFR exome AF: 0.0473

Gnomad AMR exome AF: 0.169

Gnomad ASJ exome AF: 0.131

Gnomad EAS exome AF: 0.0180

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.161

Gnomad OTH exome AF: 0.146

GnomAD4 exome AF: 0.144 AC: 209559 AN: 1459548 Hom.: 16247 Cov.: 31 AF XY: 0.141 AC XY: 102532 AN XY: 726080

African (AFR) AF: 0.0420 AC: 1405 AN: 33424

American (AMR) AF: 0.171 AC: 7571 AN: 44308

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 3467 AN: 26086

East Asian (EAS) AF: 0.0152 AC: 602 AN: 39642

South Asian (SAS) AF: 0.0584 AC: 5024 AN: 86042

European-Finnish (FIN) AF: 0.119 AC: 6350 AN: 53364

Middle Eastern (MID) AF: 0.128 AC: 737 AN: 5766

European-Non Finnish (NFE) AF: 0.159 AC: 176130 AN: 1110618

Other (OTH) AF: 0.137 AC: 8273 AN: 60298

GnomAD4 genome AF: 0.118 AC: 17925 AN: 152276 Hom.: 1305 Cov.: 32 AF XY: 0.114 AC XY: 8526 AN XY: 74464

African (AFR) AF: 0.0469 AC: 1951 AN: 41580

American (AMR) AF: 0.179 AC: 2742 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 441 AN: 3470

East Asian (EAS) AF: 0.0168 AC: 87 AN: 5182

South Asian (SAS) AF: 0.0501 AC: 242 AN: 4830

European-Finnish (FIN) AF: 0.105 AC: 1116 AN: 10608

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10917 AN: 68010

Other (OTH) AF: 0.143 AC: 302 AN: 2114

Alfa AF: 0.148 Hom.: 3762

Bravo AF: 0.121

Asia WGS AF: 0.0370 AC: 128 AN: 3478

EpiCase AF: 0.155

EpiControl AF: 0.164

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.9
DANN	Benign	0.52
PhyloP100		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=90/10	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: rs17215796; hg19: chr9-14662260; COSMIC: COSV66612888;