Variant 19-52065184-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001136499.2(ZNF841):c.2698G>A(p.Ala900Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000681 in 1,601,754 control chromosomes in the GnomAD database, including 4 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000072 ( 4 hom. )

Consequence

ZNF841
NM_001136499.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.341

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009257078).

BP6

Variant 19-52065184-C-T is Benign according to our data. Variant chr19-52065184-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2244091.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF841	NM_001136499.2 linkuse as main transcript	c.2698G>A	p.Ala900Thr	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.2698G>A	p.Ala900Thr	missense_variant	7/7	3	NM_001136499.2	ENSP00000470100.2		Q6ZN19-3M0QYV6

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152196

Hom.:

Cov.:

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:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000913

AC:

AN:

240944

Hom.:

AF XY:

0.000107

AC XY:

AN XY:

130366

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000634

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000366

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000717

AC:

104

AN:

1449558

Hom.:

Cov.:

AF XY:

0.0000903

AC XY:

AN XY:

720002

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000725

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000344

Gnomad4 OTH exome

AF:

0.0000835

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74356

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:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000794

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.0000742

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.44

DANN

Benign

0.90

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0043

LIST_S2

Benign

0.066

T;.;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.0093

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.9

.;.;N

PrimateAI

Benign

0.25

PROVEAN

Benign

1.5

N;.;N

REVEL

Benign

0.017

Sift

Benign

1.0

T;.;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.033

MVP

0.076

MPC

0.13

ClinPred

0.025

GERP RS

-1.0

Varity_R

0.020

gMVP

0.011

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