Variant chr19-43873461-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001033719.3(ZNF404):c.753G>A(p.Thr251Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00368 in 1,613,458 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 19 hom. )

Consequence

ZNF404
NM_001033719.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.936

Variant links:

Genes affected

ZNF404 (HGNC:19417): (zinc finger protein 404) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF404 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 19-43873461-C-T is Benign according to our data. Variant chr19-43873461-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2650073.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.936 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF404	NM_001033719.3 link	c.753G>A	p.Thr251Thr	synonymous_variant	3/3	ENST00000587539.2	NP_001028891.2	Q494X3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF404	ENST00000587539.2 link	c.753G>A	p.Thr251Thr	synonymous_variant	3/3	5	NM_001033719.3	ENSP00000466051.1		Q494X3

Frequencies

GnomAD3 genomes

AF:

0.00316

AC:

480

AN:

151978

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000894

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00793

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00464

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00326

AC:

812

AN:

249210

Hom.:

AF XY:

0.00312

AC XY:

422

AN XY:

135152

show subpopulations

Gnomad AFR exome

AF:

0.000774

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00203

Gnomad SAS exome

AF:

0.00101

Gnomad FIN exome

AF:

0.00663

Gnomad NFE exome

AF:

0.00460

Gnomad OTH exome

AF:

0.00199

GnomAD4 exome

AF:

0.00374

AC:

5462

AN:

1461362

Hom.:

Cov.:

AF XY:

0.00363

AC XY:

2639

AN XY:

726946

show subpopulations

Gnomad4 AFR exome

AF:

0.000956

Gnomad4 AMR exome

AF:

0.00168

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00136

Gnomad4 SAS exome

AF:

0.000916

Gnomad4 FIN exome

AF:

0.00639

Gnomad4 NFE exome

AF:

0.00426

Gnomad4 OTH exome

AF:

0.00239

GnomAD4 genome

AF:

0.00316

AC:

480

AN:

152096

Hom.:

Cov.:

AF XY:

0.00323

AC XY:

240

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.000891

Gnomad4 AMR

AF:

0.00210

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00793

Gnomad4 NFE

AF:

0.00464

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00374

Hom.:

Bravo

AF:

0.00231

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00349

EpiControl

AF:

0.00409

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

ZNF404: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.9

DANN

Benign

0.29

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