Variant 12-76815159-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015336.4(ZDHHC17):c.557T>C(p.Met186Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000128 in 1,563,398 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 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000099 ( 0 hom. )

Consequence

ZDHHC17
NM_015336.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.79

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19014192).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC17	NM_015336.4 linkuse as main transcript	c.557T>C	p.Met186Thr	missense_variant	6/17	ENST00000426126.7
ZDHHC17	NM_001359626.1 linkuse as main transcript	c.527T>C	p.Met176Thr	missense_variant	6/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC17	ENST00000426126.7 linkuse as main transcript	c.557T>C	p.Met186Thr	missense_variant	6/17	1	NM_015336.4	P1	Q8IUH5-1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151880

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:

0.0000885

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

182502

Hom.:

AF XY:

0.0000103

AC XY:

AN XY:

96886

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:

0.0000398

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000992

AC:

AN:

1411518

Hom.:

Cov.:

AF XY:

0.0000100

AC XY:

AN XY:

697674

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:

0.0000129

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151880

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74174

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:

0.0000885

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.00000846

AC:

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

Jun 16, 2024

The c.557T>C (p.M186T) alteration is located in exon 6 (coding exon 6) of the ZDHHC17 gene. This alteration results from a T to C substitution at nucleotide position 557, causing the methionine (M) at amino acid position 186 to be replaced by a threonine (T). 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

Uncertain

0.40

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.10

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.043

T;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.031

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.73

N;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

0.18

N;N

REVEL

Benign

0.28

Sift

Benign

0.67

T;T

Sift4G

Benign

0.41

T;T

Polyphen

0.017

B;.

Vest4

0.54

MVP

0.57

MPC

1.3

ClinPred

0.73

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.54

gMVP

0.48

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

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