Variant 19-20006013-T-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_033196.3(ZNF682):c.1489A>C(p.Thr497Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,421,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000014 ( 0 hom. )

Consequence

ZNF682
NM_033196.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.487

Variant links:

Genes affected

ZNF682 (HGNC:28857): (zinc finger protein 682) 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF682 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=0.1997917).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF682	NM_033196.3 linkuse as main transcript	c.1489A>C	p.Thr497Pro	missense_variant	4/4	ENST00000397165.7	NP_149973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF682	ENST00000397165.7 linkuse as main transcript	c.1489A>C	p.Thr497Pro	missense_variant	4/4	2	NM_033196.3	ENSP00000380351	P2	O95780-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1421266

Hom.:

Cov.:

AF XY:

0.00000285

AC XY:

AN XY:

702658

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:

0.00000183

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000471

Hom.:

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 06, 2022

The c.1489A>C (p.T497P) alteration is located in exon 4 (coding exon 4) of the ZNF682 gene. This alteration results from a A to C substitution at nucleotide position 1489, causing the threonine (T) at amino acid position 497 to be replaced by a proline (P). 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

0.078

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.043

.;T;.;.;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.26

T;T;.;T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.20

T;T;T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Pathogenic

3.3

.;M;.;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.9

D;D;D;.;.

REVEL

Benign

0.031

Sift

Uncertain

0.0010

D;D;D;.;.

Sift4G

Pathogenic

0.0010

D;D;D;D;D

Polyphen

0.97

.;D;.;.;.

Vest4

0.084

MutPred

0.26

.;Loss of glycosylation at T497 (P = 0.0631);.;.;.;

MVP

0.77

MPC

0.071

ClinPred

0.45

GERP RS

1.1

Varity_R

0.34

gMVP

0.025

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