Variant 19-52553302-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001039886.4(ZNF808):c.386C>T(p.Thr129Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000636 in 1,613,518 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00064 ( 1 hom. )

Consequence

ZNF808
NM_001039886.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.12

Variant links:

Genes affected

ZNF808 (HGNC:33230): (zinc finger protein 808) 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]

ZNF808 links:

ZNF808 (HGNC:):

ZNF808 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008458167).

BP6

Variant 19-52553302-C-T is Benign according to our data. Variant chr19-52553302-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2341300.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF808	NM_001039886.4 linkuse as main transcript	c.386C>T	p.Thr129Met	missense_variant	5/5	ENST00000359798.9	NP_001034975.2	Q8N4W9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF808	ENST00000359798.9 linkuse as main transcript	c.386C>T	p.Thr129Met	missense_variant	5/5	5	NM_001039886.4	ENSP00000352846.4		Q8N4W9-1

Frequencies

GnomAD3 genomes

AF:

0.000585

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000946

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000542

AC:

136

AN:

251012

Hom.:

AF XY:

0.000575

AC XY:

AN XY:

135660

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.000377

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000907

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000641

AC:

937

AN:

1461318

Hom.:

Cov.:

AF XY:

0.000627

AC XY:

456

AN XY:

726934

show subpopulations

Gnomad4 AFR exome

AF:

0.000689

Gnomad4 AMR exome

AF:

0.000381

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000773

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.000585

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000946

Gnomad4 NFE

AF:

0.000823

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000491

Hom.:

Bravo

AF:

0.000601

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000675

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

Oct 20, 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

0.066

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.13

DANN

Benign

0.040

DEOGEN2

Benign

0.00097

T;.;.;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.00030

LIST_S2

Benign

0.70

T;T;T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.0085

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-2.3

N;.;.;.

PrimateAI

Benign

0.22

PROVEAN

Benign

3.5

N;N;N;N

REVEL

Benign

0.037

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.44

T;T;T;T

Polyphen

0.0

B;.;.;.

Vest4

0.066

MVP

0.21

MPC

0.098

ClinPred

0.0055

GERP RS

-1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.010

gMVP

0.017

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