19-52155293-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001102657.3(ZNF836):​c.2390G>A​(p.Arg797Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000806 in 1,613,496 control chromosomes in the GnomAD database, including 1 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R797W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000082 ( 1 hom. )

Consequence

ZNF836
NM_001102657.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -1.73
Variant links:
Genes affected
ZNF836 (HGNC:34333): (zinc finger protein 836) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03143829).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF836NM_001102657.3 linkc.2390G>A p.Arg797Gln missense_variant Exon 5 of 5 ENST00000682614.1 NP_001096127.1 Q6ZNA1
ZNF836XM_011526558.4 linkc.2390G>A p.Arg797Gln missense_variant Exon 5 of 5 XP_011524860.1 Q6ZNA1
ZNF836XM_011526559.4 linkc.2390G>A p.Arg797Gln missense_variant Exon 4 of 4 XP_011524861.1 Q6ZNA1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF836ENST00000682614.1 linkc.2390G>A p.Arg797Gln missense_variant Exon 5 of 5 NM_001102657.3 ENSP00000507838.1 Q6ZNA1
ZNF836ENST00000597252.5 linkc.2390G>A p.Arg797Gln missense_variant Exon 5 of 5 2 ENSP00000470239.1 Q6ZNA1
ENSG00000267827ENST00000594362.1 linkn.554+5172G>A intron_variant Intron 4 of 4 5
ENSG00000267827ENST00000598982.5 linkn.494+5172G>A intron_variant Intron 4 of 4 4

Frequencies

GnomAD3 genomes
AF:
0.0000659
AC:
10
AN:
151846
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.000118
Gnomad OTH
AF:
0.000958
GnomAD3 exomes
AF:
0.0000798
AC:
20
AN:
250594
Hom.:
0
AF XY:
0.0000958
AC XY:
13
AN XY:
135650
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000202
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000882
Gnomad OTH exome
AF:
0.000329
GnomAD4 exome
AF:
0.0000821
AC:
120
AN:
1461534
Hom.:
1
Cov.:
34
AF XY:
0.0000798
AC XY:
58
AN XY:
727072
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000792
Gnomad4 OTH exome
AF:
0.000215
GnomAD4 genome
AF:
0.0000658
AC:
10
AN:
151962
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74278
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.000118
Gnomad4 OTH
AF:
0.000948
Alfa
AF:
0.000147
Hom.:
0
Bravo
AF:
0.0000756
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.000164
EpiControl
AF:
0.000178

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 16, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2390G>A (p.R797Q) alteration is located in exon 5 (coding exon 3) of the ZNF836 gene. This alteration results from a G to A substitution at nucleotide position 2390, causing the arginine (R) at amino acid position 797 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided Uncertain:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.085
BayesDel_addAF
Benign
-0.63
T
BayesDel_noAF
Benign
-0.86
CADD
Benign
4.3
DANN
Benign
0.23
DEOGEN2
Benign
0.0025
T;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.00040
N
LIST_S2
Benign
0.79
T;T
M_CAP
Benign
0.00075
T
MetaRNN
Benign
0.031
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
-0.15
N;.
PrimateAI
Benign
0.20
T
PROVEAN
Benign
0.79
.;N
REVEL
Benign
0.018
Sift
Benign
1.0
.;T
Sift4G
Benign
1.0
T;T
Polyphen
0.031
B;.
Vest4
0.045
MVP
0.061
MPC
0.31
ClinPred
0.027
T
GERP RS
0.71
Varity_R
0.015
gMVP
0.024

Splicing

Name
Calibrated prediction
Score
Prediction
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: rs369202646; hg19: chr19-52658546; COSMIC: COSV100440567; COSMIC: COSV100440567; API