Variant 3-42914365-A-G 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_207404.4(ZNF662):c.292A>G(p.Lys98Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000243 in 1,606,230 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 0.000086 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ZNF662
NM_207404.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0530

Variant links:

Genes affected

ZNF662 (HGNC:31930): (zinc finger protein 662) Predicted to enable DNA-binding transcription factor activity 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 located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF662 links:

Genome browser will be placed here

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=0.06735453).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF662	NM_207404.4 linkuse as main transcript	c.292A>G	p.Lys98Glu	missense_variant	5/5	ENST00000440367.7	NP_997287.2
ZNF662	NM_001134656.2 linkuse as main transcript	c.370A>G	p.Lys124Glu	missense_variant	4/4		NP_001128128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF662	ENST00000440367.7 linkuse as main transcript	c.292A>G	p.Lys98Glu	missense_variant	5/5	2	NM_207404.4	ENSP00000405047		Q6ZS27-1
ZNF662	ENST00000328199.6 linkuse as main transcript	c.370A>G	p.Lys124Glu	missense_variant	4/4	5		ENSP00000329264	P1	Q6ZS27-3
ZNF662	ENST00000422021.1 linkuse as main transcript	c.152-3084A>G		intron_variant		2		ENSP00000408945
ZNF662	ENST00000475386.1 linkuse as main transcript	n.1195A>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0000856

AC:

AN:

151846

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000854

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000824

AC:

AN:

242664

Hom.:

AF XY:

0.0000686

AC XY:

AN XY:

131158

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000615

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:

0.00

GnomAD4 exome

AF:

0.0000179

AC:

AN:

1454384

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

723256

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000609

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000856

AC:

AN:

151846

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74140

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000854

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000831

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

Aug 26, 2022

The c.370A>G (p.K124E) alteration is located in exon 4 (coding exon 4) of the ZNF662 gene. This alteration results from a A to G substitution at nucleotide position 370, causing the lysine (K) at amino acid position 124 to be replaced by a glutamic acid (E). 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

0.13

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0072

T;.

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.0027

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.067

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.74

N;N

REVEL

Benign

0.084

Sift

Benign

0.069

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.90

P;.

Vest4

0.27

MutPred

0.46

Loss of methylation at K98 (P = 0.0057);.;

MVP

0.59

MPC

0.28

ClinPred

0.066

GERP RS

2.9

Varity_R

0.091

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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