Variant 5-819542-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_024786.3(ZDHHC11):c.1129G>A(p.Gly377Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000711 in 1,609,788 control chromosomes in the GnomAD database, including 46 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 Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.

Frequency

Genomes: 𝑓 0.00042 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00074 ( 43 hom. )

Consequence

ZDHHC11
NM_024786.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.73

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03802371).

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC11	NM_024786.3 linkuse as main transcript	c.1129G>A	p.Gly377Arg	missense_variant	10/13	ENST00000283441.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC11	ENST00000283441.13 linkuse as main transcript	c.1129G>A	p.Gly377Arg	missense_variant	10/13	1	NM_024786.3	P1	Q9H8X9-1
ZDHHC11	ENST00000503758.6 linkuse as main transcript	n.2831G>A		non_coding_transcript_exon_variant	9/12	5
ZDHHC11	ENST00000507800.1 linkuse as main transcript	c.*751G>A		3_prime_UTR_variant, NMD_transcript_variant	9/12	5

Frequencies

GnomAD3 genomes

AF:

0.000422

AC:

AN:

151594

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000968

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:

0.0000951

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000871

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000339

AC:

AN:

251052

Hom.:

AF XY:

0.000361

AC XY:

AN XY:

135700

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:

0.000131

Gnomad FIN exome

AF:

0.000371

Gnomad NFE exome

AF:

0.000643

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000741

AC:

1081

AN:

1458076

Hom.:

Cov.:

AF XY:

0.000750

AC XY:

544

AN XY:

725386

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.000339

Gnomad4 NFE exome

AF:

0.000907

Gnomad4 OTH exome

AF:

0.000448

GnomAD4 genome

AF:

0.000422

AC:

AN:

151712

Hom.:

Cov.:

AF XY:

0.000458

AC XY:

AN XY:

74172

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000951

Gnomad4 NFE

AF:

0.000871

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000657

Hom.:

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000932

AC:

ExAC

AF:

0.000330

AC:

EpiCase

AF:

0.000601

EpiControl

AF:

0.000949

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

Aug 09, 2021

The c.1129G>A (p.G377R) alteration is located in exon 10 (coding exon 10) of the ZDHHC11 gene. This alteration results from a G to A substitution at nucleotide position 1129, causing the glycine (G) at amino acid position 377 to be replaced by an arginine (R). 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

0.12

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0032

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.00031

LIST_S2

Benign

0.47

M_CAP

Benign

0.0020

MetaRNN

Benign

0.038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.63

REVEL

Benign

0.064

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.17

MutPred

0.19

Loss of sheet (P = 0.0357);

MVP

0.24

MPC

0.38

ClinPred

0.073

GERP RS

-0.84

Varity_R

0.14

gMVP

0.033

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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