Variant 19-43847663-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_181845.2(ZNF283):c.1062G>A(p.Lys354=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 1,613,708 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 11 hom. )

Consequence

ZNF283
NM_181845.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0760

Variant links:

Genes affected

ZNF283 (HGNC:13077): (zinc finger protein 283) 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]

ZNF283 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 19-43847663-G-A is Benign according to our data. Variant chr19-43847663-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2650072.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.076 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00269 (3929/1461560) while in subpopulation MID AF= 0.0191 (110/5762). AF 95% confidence interval is 0.0162. There are 11 homozygotes in gnomad4_exome. There are 2003 alleles in male gnomad4_exome subpopulation. Median coverage is 65. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF283	NM_181845.2 linkuse as main transcript	c.1062G>A	p.Lys354=	synonymous_variant	7/7	ENST00000618787.5	NP_862828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF283	ENST00000618787.5 linkuse as main transcript	c.1062G>A	p.Lys354=	synonymous_variant	7/7	2	NM_181845.2	ENSP00000484852	A2
ZNF283	ENST00000324461.9 linkuse as main transcript	c.1062G>A	p.Lys354=	synonymous_variant	4/4	1		ENSP00000327314	A2
ZNF283	ENST00000650832.1 linkuse as main transcript	c.954G>A	p.Lys318=	synonymous_variant	7/7			ENSP00000498705	P2
ZNF283	ENST00000588797.6 linkuse as main transcript	c.*662G>A		3_prime_UTR_variant	6/6	2		ENSP00000468708

Frequencies

GnomAD3 genomes

AF:

0.00216

AC:

329

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00302

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00236

AC:

590

AN:

250210

Hom.:

AF XY:

0.00259

AC XY:

352

AN XY:

135680

show subpopulations

Gnomad AFR exome

AF:

0.000450

Gnomad AMR exome

AF:

0.00205

Gnomad ASJ exome

AF:

0.00437

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00121

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.00348

Gnomad OTH exome

AF:

0.00461

GnomAD4 exome

AF:

0.00269

AC:

3929

AN:

1461560

Hom.:

Cov.:

AF XY:

0.00275

AC XY:

2003

AN XY:

727078

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.00226

Gnomad4 ASJ exome

AF:

0.00467

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00130

Gnomad4 FIN exome

AF:

0.000768

Gnomad4 NFE exome

AF:

0.00291

Gnomad4 OTH exome

AF:

0.00315

GnomAD4 genome

AF:

0.00216

AC:

329

AN:

152148

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

139

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00302

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00273

Hom.:

Bravo

AF:

0.00235

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00464

EpiControl

AF:

0.00433

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

Sep 01, 2022

ZNF283: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

4.9

DANN

Benign

0.65

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