19-52155294-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001102657.3(ZNF836):c.2389C>T(p.Arg797Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,613,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. R797Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

ZNF836
NM_001102657.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.450

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]

ZNF836 links:

ENSG00000267827 (HGNC:):

ENSG00000267827 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02108854).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF836	NM_001102657.3 link	c.2389C>T	p.Arg797Trp	missense_variant	Exon 5 of 5	ENST00000682614.1	NP_001096127.1	Q6ZNA1
ZNF836	XM_011526558.4 link	c.2389C>T	p.Arg797Trp	missense_variant	Exon 5 of 5		XP_011524860.1	Q6ZNA1
ZNF836	XM_011526559.4 link	c.2389C>T	p.Arg797Trp	missense_variant	Exon 4 of 4		XP_011524861.1	Q6ZNA1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF836	ENST00000682614.1 link	c.2389C>T	p.Arg797Trp	missense_variant	Exon 5 of 5		NM_001102657.3	ENSP00000507838.1	Q6ZNA1
ZNF836	ENST00000597252.5 link	c.2389C>T	p.Arg797Trp	missense_variant	Exon 5 of 5	2		ENSP00000470239.1	Q6ZNA1
ENSG00000267827	ENST00000594362.1 link	n.554+5171C>T		intron_variant	Intron 4 of 4	5
ENSG00000267827	ENST00000598982.5 link	n.494+5171C>T		intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000758

AC:

AN:

250662

AF XY:

0.0000369

show subpopulations

Gnomad AFR exome

AF:

0.000691

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000328

AC:

AN:

1461520

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

727066

show subpopulations

African (AFR)

AF:

0.000628

AC:

AN:

33454

American (AMR)

AF:

0.0000671

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.000104

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1111746

Other (OTH)

AF:

0.0000166

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000164

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.000482

AC:

AN:

41534

American (AMR)

AF:

0.000262

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000613

Hom.:

Bravo

AF:

0.000181

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000132

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 25, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2389C>T (p.R797W) alteration is located in exon 5 (coding exon 3) of the ZNF836 gene. This alteration results from a C to T substitution at nucleotide position 2389, causing the arginine (R) at amino acid position 797 to be replaced by a tryptophan (W). 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

0.13

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.14

T;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.0035

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.00081

MetaRNN

Benign

0.021

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

2.0

M;.

PhyloP100

0.45

PrimateAI

Benign

0.22

PROVEAN

Benign

-2.3

.;N

REVEL

Benign

0.026

Sift

Benign

0.12

.;T

Sift4G

Uncertain

0.041

D;D

Polyphen

0.0080

B;.

Vest4

0.16

MVP

0.15

MPC

0.14

ClinPred

0.037

GERP RS

-0.71

Varity_R

0.055

gMVP

0.090

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

19-52155294-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over