Variant 7-65399049-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000328747.12(ZNF92):c.935C>T(p.Pro312Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

ZNF92
ENST00000328747.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

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=0.16956696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF92	NM_152626.4 linkuse as main transcript	c.935C>T	p.Pro312Leu	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 linkuse as main transcript	c.935C>T	p.Pro312Leu	missense_variant	4/4	1	NM_152626.4	ENSP00000332595.8	Q03936-1
ZNF92	ENST00000357512.3 linkuse as main transcript	c.839C>T	p.Pro280Leu	missense_variant	3/3	1		ENSP00000350113.2	Q03936-3
ZNF92	ENST00000450302.2 linkuse as main transcript	c.728C>T	p.Pro243Leu	missense_variant	3/3	1		ENSP00000396126.2	Q03936-2
ZNF92	ENST00000431504.1 linkuse as main transcript	c.707C>T	p.Pro236Leu	missense_variant	2/2	1		ENSP00000400495.1	C9IZS8

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151882

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000805

AC:

AN:

248514

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134822

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1461226

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726912

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:

0.0000243

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151882

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74178

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

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

May 14, 2024

The c.935C>T (p.P312L) alteration is located in exon 4 (coding exon 4) of the ZNF92 gene. This alteration results from a C to T substitution at nucleotide position 935, causing the proline (P) at amino acid position 312 to be replaced by a leucine (L). 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

0.23

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

T;.;.;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.14

T;T;T;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.8

L;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.26

PROVEAN

Pathogenic

-9.3

D;D;D;D

REVEL

Benign

0.097

Sift

Benign

0.12

T;T;T;T

Sift4G

Benign

0.062

T;D;T;T

Polyphen

0.99

D;P;.;.

Vest4

0.19

MutPred

0.48

Loss of disorder (P = 0.0381);.;.;.;

MVP

0.29

MPC

0.60

ClinPred

0.98

GERP RS

0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.011

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