Variant 16-67398269-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001323627.2(ZDHHC1):c.870G>T(p.Glu290Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ZDHHC1
NM_001323627.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.530

Variant links:

Genes affected

ZDHHC1 (HGNC:17916): (zinc finger DHHC-type containing 1) Enables palmitoyltransferase activity. Involved in antiviral innate immune response; positive regulation of defense response to virus by host; and protein palmitoylation. Located in Golgi apparatus and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ZDHHC1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12531361).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC1	NM_001323627.2 linkuse as main transcript	c.870G>T	p.Glu290Asp	missense_variant	8/12	ENST00000565726.3	NP_001310556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZDHHC1	ENST00000565726.3 linkuse as main transcript	c.870G>T	p.Glu290Asp	missense_variant	8/12	5	NM_001323627.2	ENSP00000459264	P1
ZDHHC1	ENST00000348579.6 linkuse as main transcript	c.870G>T	p.Glu290Asp	missense_variant	8/11	1		ENSP00000340299
ZDHHC1	ENST00000562122.1 linkuse as main transcript	n.488G>T		non_coding_transcript_exon_variant	5/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251312

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461802

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Dec 13, 2023

The c.870G>T (p.E290D) alteration is located in exon 8 (coding exon 7) of the ZDHHC1 gene. This alteration results from a G to T substitution at nucleotide position 870, causing the glutamic acid (E) at amino acid position 290 to be replaced by an aspartic acid (D). 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

-0.32

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

.;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N

MutationTaster

Benign

0.75

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.6

.;N

REVEL

Benign

0.022

Sift

Benign

0.050

.;D

Sift4G

Benign

0.14

.;T

Polyphen

0.35

.;B

Vest4

0.18

MutPred

0.31

Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);

MVP

0.35

MPC

0.17

ClinPred

0.12

GERP RS

3.1

Varity_R

0.11

gMVP

0.39

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