rs12355831

Variant names:

• chr10-112442768-A-G
• rs12355831
• NM_022494.3:c.360-417T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022494.3(ZDHHC6):​c.360-417T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0774 in 152,232 control chromosomes in the GnomAD database, including 580 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 0.077 (580 hom., cov: 32)
• Consequence: ZDHHC6 NM_022494.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.559
• Publications: 12 publications found

Genes affected

ZDHHC6 (HGNC:19160): (zinc finger DHHC-type palmitoyltransferase 6) Enables palmitoyltransferase activity. Involved in positive regulation of mitochondrial fusion and protein palmitoylation. Located in endoplasmic reticulum. [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=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC6	NM_022494.3	c.360-417T>C		intron_variant	Intron 3 of 10	ENST00000369405.7	NP_071939.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZDHHC6	ENST00000369405.7	c.360-417T>C		intron_variant	Intron 3 of 10	1	NM_022494.3	ENSP00000358413.3

Frequencies

GnomAD3 genomes AF: 0.0774 AC: 11775 AN: 152114 Hom.: 579 Cov.: 32

Gnomad AFR AF: 0.0642

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.0381

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.0122

Gnomad SAS AF: 0.0282

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0894

Gnomad OTH AF: 0.0649

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

GnomAD4 genome AF: 0.0774 AC: 11784 AN: 152232 Hom.: 580 Cov.: 32 AF XY: 0.0790 AC XY: 5876 AN XY: 74426

African (AFR) AF: 0.0642 AC: 2668 AN: 41554

American (AMR) AF: 0.0380 AC: 582 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0271 AC: 94 AN: 3470

East Asian (EAS) AF: 0.0122 AC: 63 AN: 5164

South Asian (SAS) AF: 0.0282 AC: 136 AN: 4820

European-Finnish (FIN) AF: 0.177 AC: 1875 AN: 10594

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0894 AC: 6078 AN: 68008

Other (OTH) AF: 0.0643 AC: 136 AN: 2116

Alfa AF: 0.0803 Hom.: 838

Bravo AF: 0.0664

Asia WGS AF: 0.0270 AC: 94 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	4.0
DANN	Benign	0.74
PhyloP100		0.56
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: rs12355831; hg19: chr10-114202526;