rs2306159

Variant names:

• chr10-112440597-G-A
• rs2306159
• NM_022494.3:c.618C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_022494.3(ZDHHC6):​c.618C>T​(p.Thr206Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 1,612,808 control chromosomes in the GnomAD database, including 276,110 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 0.53 (21615 hom., cov: 32)
  • Exomes 𝑓: 0.59 (254495 hom.)
• Consequence: ZDHHC6 NM_022494.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446
• Publications: 28 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP7: Synonymous conserved (PhyloP=0.446 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022494.3. 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
	ZDHHC6	NM_022494.3	MANE Select	c.618C>T	p.Thr206Thr	synonymous	Exon 5 of 11	NP_071939.1	Q9H6R6-1
	ZDHHC6	NM_001351082.3		c.618C>T	p.Thr206Thr	synonymous	Exon 5 of 11	NP_001338011.1	Q9H6R6-1
	ZDHHC6	NM_001351083.2		c.618C>T	p.Thr206Thr	synonymous	Exon 5 of 11	NP_001338012.1	Q9H6R6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC6	ENST00000369405.7	TSL:1 MANE Select	c.618C>T	p.Thr206Thr	synonymous	Exon 5 of 11	ENSP00000358413.3	Q9H6R6-1
	ZDHHC6	ENST00000369404.3	TSL:1	c.606C>T	p.Thr202Thr	synonymous	Exon 5 of 11	ENSP00000358412.3	Q9H6R6-2
	ZDHHC6	ENST00000682055.1		c.702C>T	p.Thr234Thr	synonymous	Exon 6 of 12	ENSP00000507388.1	A0A804HJ80

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79783 AN: 151826 Hom.: 21609 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.525

GnomAD2 exomes AF: 0.568 AC: 142750 AN: 251104 AF XY: 0.569

Gnomad AFR exome AF: 0.381

Gnomad AMR exome AF: 0.659

Gnomad ASJ exome AF: 0.458

Gnomad EAS exome AF: 0.437

Gnomad FIN exome AF: 0.585

Gnomad NFE exome AF: 0.587

Gnomad OTH exome AF: 0.568

GnomAD4 exome AF: 0.587 AC: 858062 AN: 1460864 Hom.: 254495 Cov.: 50 AF XY: 0.588 AC XY: 427596 AN XY: 726726

African (AFR) AF: 0.374 AC: 12488 AN: 33430

American (AMR) AF: 0.650 AC: 29030 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 11838 AN: 26100

East Asian (EAS) AF: 0.439 AC: 17412 AN: 39640

South Asian (SAS) AF: 0.599 AC: 51535 AN: 86104

European-Finnish (FIN) AF: 0.593 AC: 31654 AN: 53376

Middle Eastern (MID) AF: 0.535 AC: 3085 AN: 5768

European-Non Finnish (NFE) AF: 0.600 AC: 666399 AN: 1111442

Other (OTH) AF: 0.574 AC: 34621 AN: 60340

GnomAD4 genome AF: 0.525 AC: 79838 AN: 151944 Hom.: 21615 Cov.: 32 AF XY: 0.527 AC XY: 39151 AN XY: 74274

African (AFR) AF: 0.385 AC: 15965 AN: 41428

American (AMR) AF: 0.593 AC: 9049 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1567 AN: 3470

East Asian (EAS) AF: 0.468 AC: 2408 AN: 5142

South Asian (SAS) AF: 0.604 AC: 2908 AN: 4818

European-Finnish (FIN) AF: 0.576 AC: 6084 AN: 10558

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39939 AN: 67954

Other (OTH) AF: 0.524 AC: 1107 AN: 2112

Alfa AF: 0.559 Hom.: 39245

Bravo AF: 0.518

Asia WGS AF: 0.553 AC: 1923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	6.1
DANN	Benign	0.60
PhyloP100		0.45
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: rs2306159; hg19: chr10-114200355; COSMIC: COSV65564423;