Variant 7-65398640-A-C 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_152626.4(ZNF92):c.526A>C(p.Lys176Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,184 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: 33)

Consequence

ZNF92
NM_152626.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.14

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:

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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=0.07015103).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF92	NM_152626.4 link	c.526A>C	p.Lys176Gln	missense_variant	4/4	ENST00000328747.12	NP_689839.1	Q03936-1V9HVY7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF92	ENST00000328747.12 link	c.526A>C	p.Lys176Gln	missense_variant	4/4	1	NM_152626.4	ENSP00000332595.8	Q03936-1
ZNF92	ENST00000357512.3 link	c.430A>C	p.Lys144Gln	missense_variant	3/3	1		ENSP00000350113.2	Q03936-3
ZNF92	ENST00000450302.2 link	c.319A>C	p.Lys107Gln	missense_variant	3/3	1		ENSP00000396126.2	Q03936-2
ZNF92	ENST00000431504.1 link	c.298A>C	p.Lys100Gln	missense_variant	2/2	1		ENSP00000400495.1	C9IZS8

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

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

Dec 22, 2023

The c.526A>C (p.K176Q) alteration is located in exon 4 (coding exon 4) of the ZNF92 gene. This alteration results from a A to C substitution at nucleotide position 526, causing the lysine (K) at amino acid position 176 to be replaced by a glutamine (Q). 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

0.11

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.12

T;.;.;.

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0053

LIST_S2

Benign

0.17

T;T;T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.070

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.74

N;.;.;.

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-2.8

D;D;D;D

REVEL

Benign

0.034

Sift

Benign

0.11

T;T;D;D

Sift4G

Benign

0.10

T;T;T;T

Polyphen

0.95

P;P;.;.

Vest4

0.078

MutPred

0.32

Loss of methylation at K176 (P = 2e-04);.;.;.;

MVP

0.10

MPC

0.63

ClinPred

0.32

GERP RS

-0.76

Varity_R

0.054

gMVP

0.0046

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