Genetic Variant ZDHHC8:c.558-84A>G (chr22-20140031-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_013373.4(ZDHHC8):c.558-84A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 1,587,060 control chromosomes in the GnomAD database, including 139,217 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 0.44 ( 15265 hom., cov: 33)

Exomes 𝑓: 0.41 ( 123952 hom. )

Consequence

ZDHHC8
NM_013373.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0330

Publications

44 publications found

Variant links:

Genes affected

ZDHHC8 (HGNC:18474): (zinc finger DHHC-type palmitoyltransferase 8) This gene encodes a four transmembrane protein that is a member of the zinc finger DHHC domain-containing protein family. The encoded protein may function as a palmitoyltransferase. Defects in this gene may be associated with a susceptibility to schizophrenia. Alternate splicing of this gene results in multiple transcript variants. A pseudogene of this gene is found on chromosome 22.[provided by RefSeq, May 2010]

ZDHHC8 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013373.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC8	NM_013373.4	MANE Select	c.558-84A>G		intron	N/A	NP_037505.1
	ZDHHC8	NM_001185024.2		c.558-84A>G		intron	N/A	NP_001171953.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZDHHC8	ENST00000334554.12	TSL:1 MANE Select	c.558-84A>G	intron	N/A	ENSP00000334490.7
ZDHHC8	ENST00000469212.5	TSL:3	n.95A>G	non_coding_transcript_exon	Exon 1 of 4
ZDHHC8	ENST00000405930.3	TSL:2	c.558-84A>G	intron	N/A	ENSP00000384716.3

Frequencies

GnomAD3 genomes

AF:

0.442

AC:

67052

AN:

151776

Hom.:

15225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.484

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.503

Gnomad ASJ

AF:

0.408

Gnomad EAS

AF:

0.673

Gnomad SAS

AF:

0.531

Gnomad FIN

AF:

0.439

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.382

Gnomad OTH

AF:

0.434

GnomAD4 exome

AF:

0.409

AC:

587580

AN:

1435166

Hom.:

123952

Cov.:

AF XY:

0.412

AC XY:

294590

AN XY:

714968

show subpopulations

African (AFR)

AF:

0.483

AC:

15953

AN:

33004

American (AMR)

AF:

0.591

AC:

26051

AN:

44082

Ashkenazi Jewish (ASJ)

AF:

0.409

AC:

10600

AN:

25932

East Asian (EAS)

AF:

0.642

AC:

25324

AN:

39422

South Asian (SAS)

AF:

0.531

AC:

45383

AN:

85510

European-Finnish (FIN)

AF:

0.429

AC:

20996

AN:

48952

Middle Eastern (MID)

AF:

0.323

AC:

1855

AN:

5738

European-Non Finnish (NFE)

AF:

0.381

AC:

415955

AN:

1093018

Other (OTH)

AF:

0.428

AC:

25463

AN:

59508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

19059

38119

57178

76238

95297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13266

26532

39798

53064

66330

<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:

0.442

AC:

67146

AN:

151894

Hom.:

15265

Cov.:

AF XY:

0.450

AC XY:

33415

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.485

AC:

20064

AN:

41398

American (AMR)

AF:

0.504

AC:

7700

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.408

AC:

1416

AN:

3468

East Asian (EAS)

AF:

0.673

AC:

3473

AN:

5160

South Asian (SAS)

AF:

0.530

AC:

2553

AN:

4814

European-Finnish (FIN)

AF:

0.439

AC:

4637

AN:

10558

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.382

AC:

25969

AN:

67904

Other (OTH)

AF:

0.436

AC:

920

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1984

3968

5952

7936

9920

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

636

1272

1908

2544

3180

<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:

0.407

Hom.:

34123

Bravo

AF:

0.449

Asia WGS

AF:

0.567

AC:

1971

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

(source)

DANN

Benign

0.50

PhyloP100

-0.033

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.46

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.46

Position offset: 14

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over