Variant chr19-43847124-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_181845.2(ZNF283):c.523T>G(p.Phe175Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000277 in 1,613,488 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

ZNF283
NM_181845.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.156

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028915286).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF283	NM_181845.2 linkuse as main transcript	c.523T>G	p.Phe175Val	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.523T>G	p.Phe175Val	missense_variant	7/7	2	NM_181845.2	A2
ZNF283	ENST00000324461.9 linkuse as main transcript	c.523T>G	p.Phe175Val	missense_variant	4/4	1		A2
ZNF283	ENST00000650832.1 linkuse as main transcript	c.415T>G	p.Phe139Val	missense_variant	7/7			P2
ZNF283	ENST00000588797.6 linkuse as main transcript	c.*123T>G		3_prime_UTR_variant	6/6	2

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000471

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000343

AC:

AN:

248034

Hom.:

AF XY:

0.000438

AC XY:

AN XY:

134628

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.000204

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.000587

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000276

AC:

404

AN:

1461174

Hom.:

Cov.:

AF XY:

0.000293

AC XY:

213

AN XY:

726830

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000314

Gnomad4 OTH exome

AF:

0.000249

GnomAD4 genome

AF:

0.000282

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000471

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000378

Hom.:

Bravo

AF:

0.000253

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000487

AC:

ExAC

AF:

0.000323

AC:

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

May 17, 2023

The c.523T>G (p.F175V) alteration is located in exon 7 (coding exon 4) of the ZNF283 gene. This alteration results from a T to G substitution at nucleotide position 523, causing the phenylalanine (F) at amino acid position 175 to be replaced by a valine (V). 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

0.10

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.23

DEOGEN2

Benign

0.0050

T;T;T

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.0044

LIST_S2

Benign

0.071

.;T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.029

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.99

L;.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.3

.;.;N

REVEL

Benign

0.031

Sift

Benign

0.45

.;.;T

Sift4G

Benign

0.50

T;T;T

Polyphen

0.43

B;.;B

Vest4

0.19

MVP

0.33

MPC

0.32

ClinPred

0.018

GERP RS

2.8

Varity_R

0.081

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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