10-112446925-C-T

Position:

• chr10-112446925-C-T

Variant summary

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

The NM_001351082.3(ZDHHC6):​c.-215+221G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0936 in 206,582 control chromosomes in the GnomAD database, including 1,101 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 0.087 (677 hom., cov: 31)
  • Exomes 𝑓: 0.11 (424 hom.)
• Consequence: ZDHHC6 NM_001351082.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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]

ZDHHC6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC6	NM_022494.3	c.-435G>A		upstream_gene_variant		ENST00000369405.7	NP_071939.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC6	ENST00000369405.7	c.-435G>A		upstream_gene_variant		1	NM_022494.3	ENSP00000358413.3

Frequencies

GnomAD3 genomes AF: 0.0866 AC: 13171 AN: 152004 Hom.: 678 Cov.: 31

Gnomad AFR AF: 0.0452

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.0991

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0765

Gnomad FIN AF: 0.0751

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0949

GnomAD4 exome AF: 0.113 AC: 6167 AN: 54460 Hom.: 424 Cov.: 0 AF XY: 0.113 AC XY: 3006 AN XY: 26674

Gnomad4 AFR exome AF: 0.0441

Gnomad4 AMR exome AF: 0.0856

Gnomad4 ASJ exome AF: 0.0955

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.0752

Gnomad4 FIN exome AF: 0.0917

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.101

GnomAD4 genome AF: 0.0866 AC: 13169 AN: 152122 Hom.: 677 Cov.: 31 AF XY: 0.0854 AC XY: 6349 AN XY: 74362

Gnomad4 AFR AF: 0.0451

Gnomad4 AMR AF: 0.0992

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.0761

Gnomad4 FIN AF: 0.0751

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.0949

Alfa AF: 0.0952 Hom.: 749

Bravo AF: 0.0879

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.86
DANN	Benign	0.91

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2277205; hg19: chr10-114206683;