Variant chr5-814773-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_024786.3(ZDHHC11):c.1169T>C(p.Ile390Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,547,974 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I390M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 2 hom. )

Consequence

ZDHHC11
NM_024786.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.12

Variant links:

Genes affected

ZDHHC11 (HGNC:19158): (zinc finger DHHC-type containing 11) Enables signaling adaptor activity. Involved in antiviral innate immune response and positive regulation of defense response to virus by host. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ZDHHC11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009483874).

BP6

Variant 5-814773-A-G is Benign according to our data. Variant chr5-814773-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2239820.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC11	NM_024786.3 linkuse as main transcript	c.1169T>C	p.Ile390Thr	missense_variant	11/13	ENST00000283441.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC11	ENST00000283441.13 linkuse as main transcript	c.1169T>C	p.Ile390Thr	missense_variant	11/13	1	NM_024786.3	P1	Q9H8X9-1
ZDHHC11	ENST00000503758.6 linkuse as main transcript	n.2871T>C		non_coding_transcript_exon_variant	10/12	5
ZDHHC11	ENST00000507800.1 linkuse as main transcript	c.*791T>C		3_prime_UTR_variant, NMD_transcript_variant	10/12	5

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

146480

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000500

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000674

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000604

Gnomad SAS

AF:

0.00177

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000168

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000220

AC:

AN:

213868

Hom.:

AF XY:

0.000275

AC XY:

AN XY:

116234

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000385

Gnomad SAS exome

AF:

0.00115

Gnomad FIN exome

AF:

0.0000479

Gnomad NFE exome

AF:

0.000120

Gnomad OTH exome

AF:

0.000205

GnomAD4 exome

AF:

0.000123

AC:

172

AN:

1401370

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

104

AN XY:

694702

show subpopulations

Gnomad4 AFR exome

AF:

0.000159

Gnomad4 AMR exome

AF:

0.0000563

Gnomad4 ASJ exome

AF:

0.0000405

Gnomad4 EAS exome

AF:

0.0000811

Gnomad4 SAS exome

AF:

0.00112

Gnomad4 FIN exome

AF:

0.0000192

Gnomad4 NFE exome

AF:

0.0000657

Gnomad4 OTH exome

AF:

0.0000691

GnomAD4 genome

AF:

0.000171

AC:

AN:

146604

Hom.:

Cov.:

AF XY:

0.000153

AC XY:

AN XY:

71858

show subpopulations

Gnomad4 AFR

AF:

0.0000499

Gnomad4 AMR

AF:

0.0000673

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000605

Gnomad4 SAS

AF:

0.00177

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000168

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000297

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 30, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.17

DANN

Benign

0.19

DEOGEN2

Benign

0.0013

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.00010

LIST_S2

Benign

0.17

M_CAP

Benign

0.0013

MetaRNN

Benign

0.0095

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.53

REVEL

Benign

0.017

Sift

Benign

0.66

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.071

MVP

0.085

MPC

0.070

ClinPred

0.0035

GERP RS

0.24

Varity_R

0.021

gMVP

0.018

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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