NM_024786.3:c.220G>A

Variant summary

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

The NM_024786.3(ZDHHC11):​c.220G>A​(p.Val74Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,392 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

ZDHHC11
NM_024786.3 missense, splice_region

Scores

2
17
Splicing: ADA: 0.0001526
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.938
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]
BRD9 (HGNC:25818): (bromodomain containing 9) Enables lysine-acetylated histone binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of SWI/SNF complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.10396162).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZDHHC11NM_024786.3 linkc.220G>A p.Val74Met missense_variant, splice_region_variant Exon 1 of 13 ENST00000283441.13 NP_079062.1 Q9H8X9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZDHHC11ENST00000283441.13 linkc.220G>A p.Val74Met missense_variant, splice_region_variant Exon 1 of 13 1 NM_024786.3 ENSP00000283441.8 Q9H8X9-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152182
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000193
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
250826
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135700
show subpopulations
Gnomad AFR exome
AF:
0.000186
Gnomad AMR exome
AF:
0.00
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:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000151
AC:
22
AN:
1461210
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
726928
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152182
Hom.:
0
Cov.:
33
AF XY:
0.0000807
AC XY:
6
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.00
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:
0.0000329
Hom.:
0
Bravo
AF:
0.0000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000165
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
4.7
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0084
T
Eigen
Benign
-0.95
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.033
N
LIST_S2
Benign
0.41
T
M_CAP
Benign
0.0029
T
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.0
L
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.097
Sift
Benign
0.085
T
Sift4G
Uncertain
0.039
D
Polyphen
0.98
D
Vest4
0.091
MVP
0.16
MPC
0.19
ClinPred
0.29
T
GERP RS
-8.1
Varity_R
0.047
gMVP
0.32

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00015
dbscSNV1_RF
Benign
0.24
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.

Other links and lift over

dbSNP: rs374151213; hg19: chr5-850498; API