Variant 7-149210690-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000610704.5(ZNF282):c.938C>T(p.Thr313Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000025 in 1,601,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

ZNF282
ENST00000610704.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.13

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:

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=0.14407468).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF282	NM_003575.4 linkuse as main transcript	c.938C>T	p.Thr313Met	missense_variant	5/8	ENST00000610704.5	NP_003566.1
ZNF282	NM_001303481.3 linkuse as main transcript	c.938C>T	p.Thr313Met	missense_variant	5/9		NP_001290410.1
ZNF282	XM_006716151.5 linkuse as main transcript	c.938C>T	p.Thr313Met	missense_variant	5/8		XP_006716214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF282	ENST00000610704.5 linkuse as main transcript	c.938C>T	p.Thr313Met	missense_variant	5/8	1	NM_003575.4	ENSP00000477841	P1	Q9UDV7-1
ZNF282	ENST00000479907.1 linkuse as main transcript	c.938C>T	p.Thr313Met	missense_variant	5/9	2		ENSP00000418840		Q9UDV7-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152202

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000215

AC:

AN:

232906

Hom.:

AF XY:

0.00000794

AC XY:

AN XY:

125970

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000572

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000284

Gnomad OTH exome

AF:

0.000180

GnomAD4 exome

AF:

0.0000269

AC:

AN:

1449330

Hom.:

Cov.:

AF XY:

0.0000264

AC XY:

AN XY:

720186

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000508

Gnomad4 SAS exome

AF:

0.0000833

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000208

Gnomad4 OTH exome

AF:

0.000100

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000194

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

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

Jun 16, 2024

The c.938C>T (p.T313M) alteration is located in exon 5 (coding exon 5) of the ZNF282 gene. This alteration results from a C to T substitution at nucleotide position 938, causing the threonine (T) at amino acid position 313 to be replaced by a methionine (M). 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

0.17

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

T;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.2

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.4

.;N

REVEL

Benign

0.070

Sift

Uncertain

0.0040

.;D

Sift4G

Benign

0.12

T;T

Polyphen

0.86

P;.

Vest4

0.38

MutPred

0.27

Loss of glycosylation at T313 (P = 0.0288);Loss of glycosylation at T313 (P = 0.0288);

MVP

0.43

ClinPred

0.18

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.041

gMVP

0.37

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