Genetic Variant ZDHHC6:n.-373G>A (chr10-112446925-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000681964.1(ZDHHC6):n.-373G>A variant causes a non coding transcript exon 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
ENST00000681964.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.49

Publications

15 publications found

Variant links:

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 links:

VTI1A (HGNC:17792): (vesicle transport through interaction with t-SNAREs 1A) The protein encoded by this gene is a member of the family of soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptors (SNAREs) that function in intracellular trafficking. This family member is involved in vesicular transport between endosomes and the trans-Golgi network. It is a vesicle-associated SNARE (v-SNARE) that interacts with target membrane SNAREs (t-SNAREs). Polymorphisms in this gene have been associated with binocular function, and also with susceptibility to colorectal and lung cancers. A recurrent rearrangement has been found between this gene and the transcription factor 7-like 2 (TCF7L2) gene in colorectal cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

VTI1A links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZDHHC6	NM_022494.3 link	c.-435G>A		upstream_gene_variant		ENST00000369405.7	NP_071939.1	Q9H6R6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZDHHC6	ENST00000369405.7 link	c.-435G>A		upstream_gene_variant		1	NM_022494.3	ENSP00000358413.3		Q9H6R6-1

Frequencies

GnomAD3 genomes

AF:

0.0866

AC:

13171

AN:

152004

Hom.:

678

Cov.:

show subpopulations

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.:

AF XY:

0.113

AC XY:

3006

AN XY:

26674

show subpopulations

African (AFR)

AF:

0.0441

AC:

AN:

2178

American (AMR)

AF:

0.0856

AC:

312

AN:

3646

Ashkenazi Jewish (ASJ)

AF:

0.0955

AC:

250

AN:

2618

East Asian (EAS)

AF:

0.184

AC:

1509

AN:

8202

South Asian (SAS)

AF:

0.0752

AC:

267

AN:

3552

European-Finnish (FIN)

AF:

0.0917

AC:

AN:

338

Middle Eastern (MID)

AF:

0.0732

AC:

AN:

246

European-Non Finnish (NFE)

AF:

0.110

AC:

3312

AN:

30014

Other (OTH)

AF:

0.101

AC:

372

AN:

3666

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

259

518

778

1037

1296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0866

AC:

13169

AN:

152122

Hom.:

677

Cov.:

AF XY:

0.0854

AC XY:

6349

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.0451

AC:

1874

AN:

41520

American (AMR)

AF:

0.0992

AC:

1517

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.104

AC:

362

AN:

3468

East Asian (EAS)

AF:

0.117

AC:

602

AN:

5130

South Asian (SAS)

AF:

0.0761

AC:

367

AN:

4820

European-Finnish (FIN)

AF:

0.0751

AC:

796

AN:

10602

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.109

AC:

7377

AN:

67982

Other (OTH)

AF:

0.0949

AC:

200

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

587

1174

1761

2348

2935

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0953

Hom.:

957

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

(source)

DANN

Benign

0.91

PhyloP100

-1.5

PromoterAI

-0.068

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over