Variant 19-43847191-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181845.2(ZNF283):c.590A>G(p.His197Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF283
NM_181845.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.59

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19578078).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF283	NM_181845.2 linkuse as main transcript	c.590A>G	p.His197Arg	missense_variant	7/7	ENST00000618787.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZNF283	ENST00000618787.5 linkuse as main transcript	c.590A>G	p.His197Arg	missense_variant	7/7	2	NM_181845.2	A2
ZNF283	ENST00000324461.9 linkuse as main transcript	c.590A>G	p.His197Arg	missense_variant	4/4	1		A2
ZNF283	ENST00000650832.1 linkuse as main transcript	c.482A>G	p.His161Arg	missense_variant	7/7			P2
ZNF283	ENST00000588797.6 linkuse as main transcript	c.*190A>G		3_prime_UTR_variant	6/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249122

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135178

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461532

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727034

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 16, 2023

The c.590A>G (p.H197R) alteration is located in exon 7 (coding exon 4) of the ZNF283 gene. This alteration results from a A to G substitution at nucleotide position 590, causing the histidine (H) at amino acid position 197 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.041

T;T;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.35

.;T;T

M_CAP

Benign

0.0047

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Pathogenic

3.3

M;.;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-4.5

.;.;D

REVEL

Benign

0.14

Sift

Benign

0.054

.;.;T

Sift4G

Uncertain

0.020

D;D;D

Polyphen

0.20

B;.;B

Vest4

0.21

MutPred

0.51

Gain of MoRF binding (P = 0.0184);.;Gain of MoRF binding (P = 0.0184);

MVP

0.55

MPC

0.39

ClinPred

0.24

GERP RS

3.5

Varity_R

0.25

gMVP

0.052

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