Variant chr5-833775-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024786.3(ZDHHC11):c.933G>C(p.Gln311His) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 151,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000026 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZDHHC11
NM_024786.3 missense, splice_region

Scores

Splicing: ADA: 0.00009036

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.51

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017148137).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC11	NM_024786.3 linkuse as main transcript	c.933G>C	p.Gln311His	missense_variant, splice_region_variant	7/13	ENST00000283441.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC11	ENST00000283441.13 linkuse as main transcript	c.933G>C	p.Gln311His	missense_variant, splice_region_variant	7/13	1	NM_024786.3	P1	Q9H8X9-1
ZDHHC11	ENST00000503758.6 linkuse as main transcript	n.1996G>C		splice_region_variant, non_coding_transcript_exon_variant	4/12	5
ZDHHC11	ENST00000508951.1 linkuse as main transcript	n.212G>C		splice_region_variant, non_coding_transcript_exon_variant	3/5	3
ZDHHC11	ENST00000507800.1 linkuse as main transcript	c.516G>C	p.Gln172His	missense_variant, splice_region_variant, NMD_transcript_variant	5/12	5

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151558

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000136

AC:

AN:

176662

Hom.:

AF XY:

0.000105

AC XY:

AN XY:

95072

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000924

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000255

AC:

AN:

1371844

Hom.:

Cov.:

AF XY:

0.0000175

AC XY:

AN XY:

685284

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000813

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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

AF:

0.00000660

AC:

AN:

151558

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73996

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000960

Hom.:

ExAC

AF:

0.0000670

AC:

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

Oct 31, 2022

The c.933G>C (p.Q311H) alteration is located in exon 7 (coding exon 7) of the ZDHHC11 gene. This alteration results from a G to C substitution at nucleotide position 933, causing the glutamine (Q) at amino acid position 311 to be replaced by a histidine (H). 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

-0.63

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.19

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0096

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.35

M_CAP

Benign

0.00084

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.1

REVEL

Benign

0.018

Sift

Benign

0.094

Sift4G

Uncertain

0.0030

Polyphen

0.0060

Vest4

0.13

MutPred

0.48

Gain of loop (P = 0.0166);

MVP

0.085

MPC

0.17

ClinPred

0.017

GERP RS

-3.0

Varity_R

0.049

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000090

dbscSNV1_RF

Benign

0.0080

SpliceAI score (max)

0.14

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