Variant 19-22663872-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000456783.3(ZNF492):c.203T>G(p.Leu68Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000038 in 1,580,404 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: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

ZNF492
ENST00000456783.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.22

Variant links:

Genes affected

ZNF492 (HGNC:23707): (zinc finger protein 492) 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]

ZNF492 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=0.21678644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF492	NM_020855.3 linkuse as main transcript	c.203T>G	p.Leu68Arg	missense_variant	4/4	ENST00000456783.3	NP_065906.1	Q9P255
ZNF492	XM_047439130.1 linkuse as main transcript	c.203T>G	p.Leu68Arg	missense_variant	4/4		XP_047295086.1
ZNF492	XM_047439131.1 linkuse as main transcript	c.107T>G	p.Leu36Arg	missense_variant	3/3		XP_047295087.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF492	ENST00000456783.3 linkuse as main transcript	c.203T>G	p.Leu68Arg	missense_variant	4/4	1	NM_020855.3	ENSP00000413660.2		Q9P255

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151558

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:

0.000194

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:

0.0000138

AC:

AN:

216900

Hom.:

AF XY:

0.00000851

AC XY:

AN XY:

117532

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000185

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:

0.00000350

AC:

AN:

1428846

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

709340

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151558

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74004

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000453

ExAC

AF:

0.0000169

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

Dec 18, 2023

The c.203T>G (p.L68R) alteration is located in exon 4 (coding exon 3) of the ZNF492 gene. This alteration results from a T to G substitution at nucleotide position 203, causing the leucine (L) at amino acid position 68 to be replaced by an arginine (R). 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

0.10

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.036

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.0018

LIST_S2

Benign

0.56

M_CAP

Benign

0.00074

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

4.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-5.0

REVEL

Benign

0.055

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.019

Polyphen

0.99

Vest4

0.25

MutPred

0.51

Loss of stability (P = 0.0664);

MVP

0.49

MPC

2.8

ClinPred

0.59

GERP RS

1.2

Varity_R

0.42

gMVP

0.020

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