Variant 19-57326690-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_213598.4(ZNF543):c.203G>A(p.Trp68*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00592 in 1,613,884 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 30 hom. )

Consequence

ZNF543
NM_213598.4 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.751

Variant links:

Genes affected

ZNF543 (HGNC:25281): (zinc finger protein 543) Predicted to enable DNA-binding transcription factor 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]

ZNF543 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant 19-57326690-G-A is Benign according to our data. Variant chr19-57326690-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 779288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF543	NM_213598.4 linkuse as main transcript	c.203G>A	p.Trp68*	stop_gained	3/4	ENST00000321545.5	NP_998763.2	Q08ER8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF543	ENST00000321545.5 linkuse as main transcript	c.203G>A	p.Trp68*	stop_gained	3/4	1	NM_213598.4	ENSP00000322545.3		Q08ER8

Frequencies

GnomAD3 genomes

AF:

0.00455

AC:

693

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00891

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00673

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00432

AC:

1085

AN:

251222

Hom.:

AF XY:

0.00407

AC XY:

553

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00695

Gnomad ASJ exome

AF:

0.00854

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00603

Gnomad OTH exome

AF:

0.00734

GnomAD4 exome

AF:

0.00607

AC:

8865

AN:

1461606

Hom.:

Cov.:

AF XY:

0.00586

AC XY:

4262

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.00673

Gnomad4 ASJ exome

AF:

0.00792

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.000487

Gnomad4 NFE exome

AF:

0.00710

Gnomad4 OTH exome

AF:

0.00560

GnomAD4 genome

AF:

0.00455

AC:

693

AN:

152278

Hom.:

Cov.:

AF XY:

0.00420

AC XY:

313

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00149

Gnomad4 AMR

AF:

0.00889

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00673

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00597

Hom.:

Bravo

AF:

0.00499

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00628

AC:

ExAC

AF:

0.00400

AC:

485

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00633

EpiControl

AF:

0.00806

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Benign

0.97

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.024

Vest4

0.026

GERP RS

-0.82

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