Variant 7-65388858-G-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_152626.4(ZNF92):c.183G>T(p.Glu61Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000342 in 1,433,666 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.000047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

ZNF92
NM_152626.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.841

Variant links:

Genes affected

ZNF92 (HGNC:13168): (zinc finger protein 92) 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]

ZNF92 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=0.040995687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF92	NM_152626.4 linkuse as main transcript	c.183G>T	p.Glu61Asp	missense_variant	3/4	ENST00000328747.12	NP_689839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF92	ENST00000328747.12 linkuse as main transcript	c.183G>T	p.Glu61Asp	missense_variant	3/4	1	NM_152626.4	ENSP00000332595	P2	Q03936-1
ZNF92	ENST00000450302.2 linkuse as main transcript	c.-25G>T		5_prime_UTR_variant	2/3	1		ENSP00000396126		Q03936-2
ZNF92	ENST00000357512.3 linkuse as main transcript	c.130+830G>T		intron_variant		1		ENSP00000350113	A2	Q03936-3
ZNF92	ENST00000431504.1 linkuse as main transcript	c.-2-9483G>T		intron_variant		1		ENSP00000400495

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149072

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000986

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000669

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:

0.0000299

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

250746

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135564

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

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:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1433666

Hom.:

Cov.:

AF XY:

0.0000280

AC XY:

AN XY:

713094

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:

0.0000420

Gnomad4 OTH exome

AF:

0.0000512

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000469

AC:

AN:

149190

Hom.:

Cov.:

AF XY:

0.0000549

AC XY:

AN XY:

72802

show subpopulations

Gnomad4 AFR

AF:

0.0000983

Gnomad4 AMR

AF:

0.0000668

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000299

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000904

Hom.:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Jan 26, 2022

The c.183G>T (p.E61D) alteration is located in exon 3 (coding exon 3) of the ZNF92 gene. This alteration results from a G to T substitution at nucleotide position 183, causing the glutamic acid (E) at amino acid position 61 to be replaced by an aspartic acid (D). 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

0.15

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.0

DANN

Benign

0.55

DEOGEN2

Benign

0.056

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.027

M_CAP

Benign

0.0030

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

D;D;D;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-2.2

REVEL

Benign

0.053

Sift

Benign

0.097

Sift4G

Benign

0.16

Polyphen

0.020

Vest4

0.079

MutPred

0.45

Loss of methylation at K60 (P = 0.0848);

MVP

0.10

MPC

0.56

ClinPred

0.032

GERP RS

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.091

gMVP

0.021

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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