Genetic Variant ZDHHC17:p.Ala165Val (chr12-76809808-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015336.4(ZDHHC17):c.494C>T(p.Ala165Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,610,300 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZDHHC17
NM_015336.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.14

Publications

0 publications found

Variant links:

Genes affected

ZDHHC17 (HGNC:18412): (zinc finger DHHC-type palmitoyltransferase 17) Enables identical protein binding activity and protein-cysteine S-palmitoyltransferase activity. Involved in lipoprotein transport and protein palmitoylation. Located in Golgi membrane; Golgi-associated vesicle membrane; and aggresome. [provided by Alliance of Genome Resources, Apr 2022]

ZDHHC17 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015336.4. 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
	ZDHHC17	NM_015336.4	MANE Select	c.494C>T	p.Ala165Val	missense	Exon 5 of 17	NP_056151.2	Q8IUH5-1
	ZDHHC17	NM_001359626.1		c.464C>T	p.Ala155Val	missense	Exon 5 of 17	NP_001346555.1	A8KA01

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZDHHC17	ENST00000426126.7	TSL:1 MANE Select	c.494C>T	p.Ala165Val	missense	Exon 5 of 17	ENSP00000403397.2	Q8IUH5-1
ZDHHC17	ENST00000968885.1		c.494C>T	p.Ala165Val	missense	Exon 5 of 18	ENSP00000638944.1
ZDHHC17	ENST00000550876.1	TSL:4	c.55-5338C>T		intron	N/A	ENSP00000449734.1	F8VX48

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458186

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725150

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33278

American (AMR)

AF:

0.00

AC:

AN:

44254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26012

East Asian (EAS)

AF:

0.00

AC:

AN:

39436

South Asian (SAS)

AF:

0.00

AC:

AN:

85648

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110318

Other (OTH)

AF:

0.00

AC:

AN:

60202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000197

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.10

CADD

Uncertain

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.13

Eigen

Benign

-0.083

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.49

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.3

PhyloP100

4.1

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.2

REVEL

Uncertain

0.29

Sift

Benign

0.61

Sift4G

Benign

0.76

Polyphen

0.17

Vest4

0.64

MutPred

0.73

Loss of helix (P = 0.1299)

MVP

0.50

MPC

1.1

ClinPred

0.93

GERP RS

5.4

Varity_R

0.35

gMVP

0.73

Mutation Taster

=25/75

disease causing

(source)

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

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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