Variant 7-65398653-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.539A>C(p.Lys180Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,459,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.0000062 ( 0 hom. )

Consequence

ZNF92
NM_152626.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.64

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 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=0.24884939).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF92	NM_152626.4 linkuse as main transcript	c.539A>C	p.Lys180Thr	missense_variant	4/4	ENST00000328747.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF92	ENST00000328747.12 linkuse as main transcript	c.539A>C	p.Lys180Thr	missense_variant	4/4	1	NM_152626.4	P2	Q03936-1
ZNF92	ENST00000357512.3 linkuse as main transcript	c.443A>C	p.Lys148Thr	missense_variant	3/3	1		A2	Q03936-3
ZNF92	ENST00000450302.2 linkuse as main transcript	c.332A>C	p.Lys111Thr	missense_variant	3/3	1			Q03936-2
ZNF92	ENST00000431504.1 linkuse as main transcript	c.311A>C	p.Lys104Thr	missense_variant	2/2	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1459944

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726196

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:

0.00000810

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 01, 2022

The c.539A>C (p.K180T) 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 539, causing the lysine (K) at amino acid position 180 to be replaced by a threonine (T). 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

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;.;.;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.63

T;T;T;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.25

T;T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Pathogenic

3.5

H;.;.;.

MutationTaster

Benign

0.80

D;D;D;D

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-5.4

D;D;D;D

REVEL

Benign

0.089

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Uncertain

0.019

D;D;D;D

Polyphen

0.25

B;P;.;.

Vest4

0.15

MutPred

0.66

Loss of methylation at K180 (P = 0.0069);.;.;.;

MVP

0.20

MPC

0.17

ClinPred

0.57

GERP RS

0.43

Varity_R

0.31

gMVP

0.016

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over