Variant 12-76827016-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_015336.4(ZDHHC17):c.1006G>A(p.Gly336Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000894 in 1,565,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000092 ( 0 hom. )

Consequence

ZDHHC17
NM_015336.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.10

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC17	NM_015336.4 linkuse as main transcript	c.1006G>A	p.Gly336Ser	missense_variant	9/17	ENST00000426126.7
ZDHHC17	NM_001359626.1 linkuse as main transcript	c.976G>A	p.Gly326Ser	missense_variant	9/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC17	ENST00000426126.7 linkuse as main transcript	c.1006G>A	p.Gly336Ser	missense_variant	9/17	1	NM_015336.4	P1	Q8IUH5-1
ZDHHC17	ENST00000546778.5 linkuse as main transcript	c.*904G>A		3_prime_UTR_variant, NMD_transcript_variant	9/9	2
ZDHHC17	ENST00000550876.1 linkuse as main transcript			downstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000195

AC:

AN:

204962

Hom.:

AF XY:

0.0000267

AC XY:

AN XY:

112370

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000401

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000920

AC:

AN:

1413720

Hom.:

Cov.:

AF XY:

0.00000855

AC XY:

AN XY:

701966

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000912

Gnomad4 OTH exome

AF:

0.0000342

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000331

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2021

The c.1006G>A (p.G336S) alteration is located in exon 9 (coding exon 9) of the ZDHHC17 gene. This alteration results from a G to A substitution at nucleotide position 1006, causing the glycine (G) at amino acid position 336 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

Eigen

Benign

0.048

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.013

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.20

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

0.18

REVEL

Benign

0.16

Sift

Uncertain

0.027

Sift4G

Benign

0.39

Polyphen

0.0

Vest4

0.51

MutPred

0.51

Loss of helix (P = 0.0072);

MVP

0.11

MPC

0.39

ClinPred

0.30

GERP RS

5.7

Varity_R

0.27

gMVP

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.21

Position offset: 34

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over