dbSNP rs201839956: ZDHHC11:p.Arg365Cys (chr5-819578-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

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

The NM_024786.3(ZDHHC11):c.1093C>T(p.Arg365Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000528 in 1,609,908 control chromosomes in the GnomAD database, including 3 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000053 ( 3 hom. )

Consequence

ZDHHC11
NM_024786.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.08

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=0.025162786).

BP6

Variant 5-819578-G-A is Benign according to our data. Variant chr5-819578-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3472835.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC11	NM_024786.3 link	c.1093C>T	p.Arg365Cys	missense_variant	Exon 10 of 13	ENST00000283441.13	NP_079062.1	Q9H8X9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZDHHC11	ENST00000283441.13 link	c.1093C>T	p.Arg365Cys	missense_variant	Exon 10 of 13	1	NM_024786.3	ENSP00000283441.8	Q9H8X9-1
ZDHHC11	ENST00000503758.6 link	n.2795C>T		non_coding_transcript_exon_variant	Exon 9 of 12	5
ZDHHC11	ENST00000507800.1 link	n.*715C>T		non_coding_transcript_exon_variant	Exon 9 of 12	5		ENSP00000423817.1	H0Y9D0
ZDHHC11	ENST00000507800.1 link	n.*715C>T		3_prime_UTR_variant	Exon 9 of 12	5		ENSP00000423817.1	H0Y9D0

Frequencies

GnomAD3 genomes

AF:

0.0000462

AC:

AN:

151506

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

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:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000115

AC:

AN:

251118

Hom.:

AF XY:

0.0000958

AC XY:

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000535

AC:

AN:

1458284

Hom.:

Cov.:

AF XY:

0.0000469

AC XY:

AN XY:

725436

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000604

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000370

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.0000462

AC:

AN:

151624

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74100

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000263

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000588

Hom.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 09, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

0.12

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.66

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0028

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00033

LIST_S2

Benign

0.37

M_CAP

Benign

0.0018

MetaRNN

Benign

0.025

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.23

REVEL

Benign

0.072

Sift

Benign

0.21

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.077

MVP

0.20

MPC

0.29

ClinPred

0.067

GERP RS

-1.0

Varity_R

0.048

gMVP

0.055

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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