Genetic Variant NM_181845.2:c.904C>T (chr19-43847505-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181845.2(ZNF283):c.904C>T(p.Arg302Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000625 in 1,601,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R302H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

ZNF283
NM_181845.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.12

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20152116).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181845.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF283	NM_181845.2	MANE Select	c.904C>T	p.Arg302Cys	missense	Exon 7 of 7	NP_862828.1	Q8N7M2
	ZNF283	NM_001297752.2		c.487C>T	p.Arg163Cys	missense	Exon 6 of 6	NP_001284681.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF283	ENST00000618787.5	TSL:2 MANE Select	c.904C>T	p.Arg302Cys	missense	Exon 7 of 7	ENSP00000484852.1	Q8N7M2
ZNF283	ENST00000324461.9	TSL:1	c.904C>T	p.Arg302Cys	missense	Exon 4 of 4	ENSP00000327314.7	Q8N7M2
ZNF283	ENST00000650832.1		c.796C>T	p.Arg266Cys	missense	Exon 7 of 7	ENSP00000498705.1	A0A494C0U8

Frequencies

GnomAD3 genomes

AF:

0.00000665

AC:

AN:

150484

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

250382

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000620

AC:

AN:

1450722

Hom.:

Cov.:

AF XY:

0.00000554

AC XY:

AN XY:

721752

show subpopulations

African (AFR)

AF:

0.0000302

AC:

AN:

33118

American (AMR)

AF:

0.0000452

AC:

AN:

44204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25824

East Asian (EAS)

AF:

0.00

AC:

AN:

39202

South Asian (SAS)

AF:

0.00

AC:

AN:

85762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00000272

AC:

AN:

1103792

Other (OTH)

AF:

0.0000502

AC:

AN:

59806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000665

AC:

AN:

150484

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73376

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40940

American (AMR)

AF:

0.00

AC:

AN:

15104

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.00

AC:

AN:

5000

South Asian (SAS)

AF:

0.00

AC:

AN:

4728

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67596

Other (OTH)

AF:

0.00

AC:

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.028

Eigen

Benign

-0.078

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.0063

LIST_S2

Benign

0.35

M_CAP

Benign

0.0038

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

PhyloP100

-1.1

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.14

Sift

Benign

0.058

Sift4G

Benign

0.23

Polyphen

1.0

Vest4

0.28

MutPred

0.65

Loss of MoRF binding (P = 0.0131)

MVP

0.47

MPC

0.95

ClinPred

0.76

GERP RS

1.9

Varity_R

0.12

gMVP

0.054

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over