chr10-112434994-G-T

Variant names:

• chr10-112434994-G-T
• rs12098576
• NM_022494.3:c.736-530C>A

Variant summary

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

The NM_022494.3(ZDHHC6):​c.736-530C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,228 control chromosomes in the GnomAD database, including 1,680 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 0.14 (1680 hom., cov: 32)
• Consequence: ZDHHC6 NM_022494.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC6	NM_022494.3	c.736-530C>A		intron_variant	Intron 6 of 10	ENST00000369405.7	NP_071939.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZDHHC6	ENST00000369405.7	c.736-530C>A		intron_variant	Intron 6 of 10	1	NM_022494.3	ENSP00000358413.3

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21681 AN: 152110 Hom.: 1680 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.142 AC: 21678 AN: 152228 Hom.: 1680 Cov.: 32 AF XY: 0.139 AC XY: 10326 AN XY: 74436

African (AFR) AF: 0.173 AC: 7194 AN: 41528

American (AMR) AF: 0.121 AC: 1851 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 387 AN: 3466

East Asian (EAS) AF: 0.0104 AC: 54 AN: 5186

South Asian (SAS) AF: 0.109 AC: 525 AN: 4824

European-Finnish (FIN) AF: 0.117 AC: 1238 AN: 10596

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9924 AN: 68010

Other (OTH) AF: 0.151 AC: 320 AN: 2116

Alfa AF: 0.0839 Hom.: 137

Bravo AF: 0.141

Asia WGS AF: 0.0760 AC: 263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.53
PhyloP100		-0.085
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: rs12098576; hg19: chr10-114194752;