dbSNP rs558892397: ZNF836:p.Ala914Val (chr19-52154942-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001102657.3(ZNF836):c.2741C>T(p.Ala914Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,425,384 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

ZNF836
NM_001102657.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.747

Publications

0 publications found

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060912013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF836	NM_001102657.3 link	c.2741C>T	p.Ala914Val	missense_variant	Exon 5 of 5	ENST00000682614.1	NP_001096127.1	Q6ZNA1
ZNF836	XM_011526558.4 link	c.2741C>T	p.Ala914Val	missense_variant	Exon 5 of 5		XP_011524860.1	Q6ZNA1
ZNF836	XM_011526559.4 link	c.2741C>T	p.Ala914Val	missense_variant	Exon 4 of 4		XP_011524861.1	Q6ZNA1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF836	ENST00000682614.1 link	c.2741C>T	p.Ala914Val	missense_variant	Exon 5 of 5		NM_001102657.3	ENSP00000507838.1		Q6ZNA1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000898

AC:

AN:

222698

AF XY:

0.00000831

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000343

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000966

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.02e-7

AC:

AN:

1425384

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

705928

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31918

American (AMR)

AF:

0.00

AC:

AN:

38508

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23864

East Asian (EAS)

AF:

0.00

AC:

AN:

39366

South Asian (SAS)

AF:

0.00

AC:

AN:

80026

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52352

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5564

European-Non Finnish (NFE)

AF:

9.13e-7

AC:

AN:

1095000

Other (OTH)

AF:

0.00

AC:

AN:

58786

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 07, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2741C>T (p.A914V) 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 2741, causing the alanine (A) at amino acid position 914 to be replaced by a valine (V). 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

0.085

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.83

CADD

Benign

8.5

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.011

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0054

LIST_S2

Benign

0.071

T;T

M_CAP

Benign

0.00087

MetaRNN

Benign

0.061

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

N;.

PhyloP100

-0.75

PrimateAI

Benign

0.20

PROVEAN

Benign

-1.3

.;N

REVEL

Benign

0.0080

Sift

Benign

0.096

.;T

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.15

B;.

Vest4

0.13

MutPred

0.32

Loss of ubiquitination at K918 (P = 0.1016);Loss of ubiquitination at K918 (P = 0.1016);

MVP

0.030

MPC

0.15

ClinPred

0.060

GERP RS

-1.3

Varity_R

0.041

gMVP

0.0064

Mutation Taster

=99/1

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

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rs558892397

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over