Variant 19-52065469-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001136499.2(ZNF841):c.2413C>T(p.Arg805Cys) 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 1,613,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

ZNF841
NM_001136499.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.41

Variant links:

Genes affected

ZNF841 (HGNC:27611): (zinc finger protein 841) 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]

ZNF841 links:

ZNF432 (HGNC:):

ZNF432 links:

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=0.16712007).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF841	NM_001136499.2 linkuse as main transcript	c.2413C>T	p.Arg805Cys	missense_variant	7/7	ENST00000594440.6	NP_001129971.1	Q6ZN19-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF841	ENST00000594440.6 linkuse as main transcript	c.2413C>T	p.Arg805Cys	missense_variant	7/7	3	NM_001136499.2	ENSP00000470100.2		Q6ZN19-3M0QYV6

Frequencies

GnomAD3 genomes

AF:

0.0000727

AC:

AN:

151400

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

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:

0.00

GnomAD3 exomes

AF:

0.0000519

AC:

AN:

250420

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.000190

Gnomad AMR exome

AF:

0.0000289

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:

0.0000618

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.0000424

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000447

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:

0.0000477

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000726

AC:

AN:

151518

Hom.:

Cov.:

AF XY:

0.0000541

AC XY:

AN XY:

73996

show subpopulations

Gnomad4 AFR

AF:

0.0000485

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:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

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

Dec 27, 2022

The c.2413C>T (p.R805C) alteration is located in exon 7 (coding exon 4) of the ZNF841 gene. This alteration results from a C to T substitution at nucleotide position 2413, causing the arginine (R) at amino acid position 805 to be replaced by a cysteine (C). 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

0.30

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.0098

LIST_S2

Uncertain

0.89

D;.;D

M_CAP

Benign

0.0015

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

.;.;M

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.3

D;.;D

REVEL

Benign

0.033

Sift

Benign

0.36

T;.;T

Sift4G

Benign

0.18

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.28

MutPred

0.46

.;.;Loss of MoRF binding (P = 0.0116);

MVP

0.39

MPC

0.20

ClinPred

0.24

GERP RS

-0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.040

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.

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