Variant chr12-76849419-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015336.4(ZDHHC17):c.1709G>A(p.Arg570Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,403,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZDHHC17
NM_015336.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.96

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2993214).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC17	NM_015336.4 linkuse as main transcript	c.1709G>A	p.Arg570Lys	missense_variant	16/17	ENST00000426126.7
ZDHHC17	NM_001359626.1 linkuse as main transcript	c.1679G>A	p.Arg560Lys	missense_variant	16/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC17	ENST00000426126.7 linkuse as main transcript	c.1709G>A	p.Arg570Lys	missense_variant	16/17	1	NM_015336.4	P1	Q8IUH5-1
ZDHHC17	ENST00000547673.1 linkuse as main transcript	n.197G>A		non_coding_transcript_exon_variant	2/2	2
ZDHHC17	ENST00000550244.1 linkuse as main transcript	n.591G>A		non_coding_transcript_exon_variant	3/4	3
ZDHHC17	ENST00000553091.5 linkuse as main transcript	n.453G>A		non_coding_transcript_exon_variant	5/5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1403934

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

693726

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:

0.0000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.25e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 27, 2022

The c.1709G>A (p.R570K) alteration is located in exon 16 (coding exon 16) of the ZDHHC17 gene. This alteration results from a G to A substitution at nucleotide position 1709, causing the arginine (R) at amino acid position 570 to be replaced by a lysine (K). 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

0.33

BayesDel_addAF

Benign

0.0024

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Benign

0.79

DEOGEN2

Benign

0.069

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.029

MetaRNN

Benign

0.30

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.065

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

0.020

REVEL

Benign

0.26

Sift

Benign

1.0

Sift4G

Benign

0.99

Polyphen

0.30

Vest4

0.53

MutPred

0.34

Loss of methylation at R570 (P = 0.0396);

MVP

0.27

MPC

1.1

ClinPred

0.57

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.89

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over