Variant 19-58356551-T-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_198458.3(ZNF497):c.1085A>G(p.Gln362Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,395,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

ZNF497
NM_198458.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.23

Variant links:

Genes affected

ZNF497 (HGNC:23714): (zinc finger protein 497) Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF497 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=0.097622246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF497	NM_198458.3 linkuse as main transcript	c.1085A>G	p.Gln362Arg	missense_variant	3/3	ENST00000311044.8
ZNF497	NM_001207009.2 linkuse as main transcript	c.1085A>G	p.Gln362Arg	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF497	ENST00000311044.8 linkuse as main transcript	c.1085A>G	p.Gln362Arg	missense_variant	3/3	2	NM_198458.3	P1
ZNF497	ENST00000425453.3 linkuse as main transcript	c.1085A>G	p.Gln362Arg	missense_variant	2/2	1		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000530

AC:

AN:

150864

Hom.:

AF XY:

0.0000609

AC XY:

AN XY:

82096

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000394

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:

0.000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000104

AC:

145

AN:

1395744

Hom.:

Cov.:

AF XY:

0.000100

AC XY:

AN XY:

689678

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000274

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000256

Gnomad4 NFE exome

AF:

0.000130

Gnomad4 OTH exome

AF:

0.0000344

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000518

Hom.:

Bravo

AF:

0.0000151

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.0000174

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

Oct 12, 2022

The c.1085A>G (p.Q362R) alteration is located in exon 3 (coding exon 1) of the ZNF497 gene. This alteration results from a A to G substitution at nucleotide position 1085, causing the glutamine (Q) at amino acid position 362 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

0.13

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.0074

T;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.047

M_CAP

Benign

0.0030

MetaRNN

Benign

0.098

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.3

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.017

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

0.35

B;B

Vest4

0.049

MVP

0.41

MPC

0.38

ClinPred

0.055

GERP RS

0.70

Varity_R

0.15

gMVP

0.033

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