Variant chr7-149198436-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_003575.4(ZNF282):c.269A>G(p.Gln90Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ZNF282
NM_003575.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.57

Variant links:

Genes affected

ZNF282 (HGNC:13076): (zinc finger protein 282) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF282 links:

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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=0.19652712).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZNF282	NM_003575.4 linkuse as main transcript	c.269A>G	p.Gln90Arg	missense_variant	2/8	ENST00000610704.5
ZNF282	NM_001303481.3 linkuse as main transcript	c.269A>G	p.Gln90Arg	missense_variant	2/9
ZNF282	XM_006716151.5 linkuse as main transcript	c.269A>G	p.Gln90Arg	missense_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF282	ENST00000610704.5 linkuse as main transcript	c.269A>G	p.Gln90Arg	missense_variant	2/8	1	NM_003575.4	P1	Q9UDV7-1
ZNF282	ENST00000479907.1 linkuse as main transcript	c.269A>G	p.Gln90Arg	missense_variant	2/9	2			Q9UDV7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727248

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 13, 2022

The c.269A>G (p.Q90R) alteration is located in exon 2 (coding exon 2) of the ZNF282 gene. This alteration results from a A to G substitution at nucleotide position 269, causing the glutamine (Q) at amino acid position 90 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

0.25

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.041

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.0096

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

0.73

N;N

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.9

.;N

REVEL

Benign

0.079

Sift

Benign

0.042

.;D

Sift4G

Benign

0.19

T;T

Polyphen

0.28

B;.

Vest4

0.53

MutPred

0.13

Gain of catalytic residue at Q90 (P = 0.0703);Gain of catalytic residue at Q90 (P = 0.0703);

MVP

0.38

ClinPred

0.64

GERP RS

4.3

Varity_R

0.13

gMVP

0.33

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over