Variant 19-43847236-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_181845.2(ZNF283):c.635G>A(p.Cys212Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,604 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 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: 0.0000021 ( 0 hom. )

Consequence

ZNF283
NM_181845.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.49

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF283	NM_181845.2 link	c.635G>A	p.Cys212Tyr	missense_variant	7/7	ENST00000618787.5	NP_862828.1	Q8N7M2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF283	ENST00000618787.5 link	c.635G>A	p.Cys212Tyr	missense_variant	7/7	2	NM_181845.2	ENSP00000484852.1	Q8N7M2
ZNF283	ENST00000324461.9 link	c.635G>A	p.Cys212Tyr	missense_variant	4/4	1		ENSP00000327314.7	Q8N7M2
ZNF283	ENST00000650832.1 link	c.527G>A	p.Cys176Tyr	missense_variant	7/7			ENSP00000498705.1	A0A494C0U8
ZNF283	ENST00000588797.6 link	c.*235G>A		3_prime_UTR_variant	6/6	2		ENSP00000468708.2	K7ESH0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249444

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135324

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:

0.000165

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461604

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.0000113

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

Oct 29, 2024

The c.635G>A (p.C212Y) alteration is located in exon 7 (coding exon 4) of the ZNF283 gene. This alteration results from a G to A substitution at nucleotide position 635, causing the cysteine (C) at amino acid position 212 to be replaced by a tyrosine (Y). 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

0.19

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.11

T;T;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.31

.;T;T

M_CAP

Benign

0.0077

MetaRNN

Uncertain

0.66

D;D;D

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.5

M;.;M

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-8.5

.;.;D

REVEL

Benign

0.22

Sift

Uncertain

0.0010

.;.;D

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

0.29

B;.;B

Vest4

0.26

MutPred

0.90

Loss of ubiquitination at K210 (P = 0.051);.;Loss of ubiquitination at K210 (P = 0.051);

MVP

0.66

MPC

0.50

ClinPred

0.78

GERP RS

2.4

Varity_R

0.74

gMVP

0.17

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