rs2306159

Positions:

• chr10-112440597-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The ENST00000369405.7(ZDHHC6):​c.618C>T​(p.Thr206=) 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 ENST00000369405.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC6	NM_022494.3	c.618C>T	p.Thr206=	synonymous_variant	5/11	ENST00000369405.7	NP_071939.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC6	ENST00000369405.7	c.618C>T	p.Thr206=	synonymous_variant	5/11	1	NM_022494.3	ENSP00000358413	P4

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

GnomAD3 exomes AF: 0.568 AC: 142750 AN: 251104 Hom.: 41592 AF XY: 0.569 AC XY: 77284 AN XY: 135714

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 SAS exome AF: 0.602

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

Gnomad4 AFR exome AF: 0.374

Gnomad4 AMR exome AF: 0.650

Gnomad4 ASJ exome AF: 0.454

Gnomad4 EAS exome AF: 0.439

Gnomad4 SAS exome AF: 0.599

Gnomad4 FIN exome AF: 0.593

Gnomad4 NFE exome AF: 0.600

Gnomad4 OTH exome AF: 0.574

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

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.524

Alfa AF: 0.563 Hom.: 32249

Bravo AF: 0.518

Asia WGS AF: 0.553 AC: 1923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	6.1
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs2306159; hg19: chr10-114200355; COSMIC: COSV65564423;