Variant 19-20007156-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_033196.3(ZNF682):c.346G>A(p.Asp116Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000301 in 1,461,370 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.000030 ( 1 hom. )

Consequence

ZNF682
NM_033196.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0270

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.041731596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF682	NM_033196.3 linkuse as main transcript	c.346G>A	p.Asp116Asn	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.346G>A	p.Asp116Asn	missense_variant	4/4	2	NM_033196.3	ENSP00000380351	P2	O95780-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000566

AC:

AN:

247288

Hom.:

AF XY:

0.0000819

AC XY:

AN XY:

134230

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000393

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1461370

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

726990

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:

0.000452

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000662

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

Jul 09, 2021

The c.346G>A (p.D116N) alteration is located in exon 4 (coding exon 4) of the ZNF682 gene. This alteration results from a G to A substitution at nucleotide position 346, causing the aspartic acid (D) at amino acid position 116 to be replaced by an asparagine (N). 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

0.081

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.0034

.;T;.;.;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.015

T;T;.;T;T;T

M_CAP

Benign

0.0010

MetaRNN

Benign

0.042

T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

2.0

.;M;.;.;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.57

N;N;N;.;.;.

REVEL

Benign

0.0090

Sift

Uncertain

0.018

D;T;D;.;.;.

Sift4G

Benign

0.38

T;T;T;T;T;.

Polyphen

0.0010

.;B;.;.;.;.

Vest4

0.10

MutPred

0.23

.;Loss of disorder (P = 0.195);.;.;.;.;

MVP

0.24

MPC

0.047

ClinPred

0.013

GERP RS

-2.2

Varity_R

0.023

gMVP

0.018

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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