Variant 19-58356707-G-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.929C>G(p.Ala310Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,415,384 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: not found (cov: 35)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF497
NM_198458.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.483

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:

ENSG00000268230 (HGNC:):

ENSG00000268230 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=0.0853993).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF497	NM_198458.3 linkuse as main transcript	c.929C>G	p.Ala310Gly	missense_variant	3/3	ENST00000311044.8	NP_940860.2	Q6ZNH5
ZNF497	NM_001207009.2 linkuse as main transcript	c.929C>G	p.Ala310Gly	missense_variant	2/2		NP_001193938.1	Q6ZNH5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF497	ENST00000311044.8 linkuse as main transcript	c.929C>G	p.Ala310Gly	missense_variant	3/3	2	NM_198458.3	ENSP00000311183.2	Q6ZNH5
ZNF497	ENST00000425453.3 linkuse as main transcript	c.929C>G	p.Ala310Gly	missense_variant	2/2	1		ENSP00000402815.2	Q6ZNH5
ENSG00000268230	ENST00000599109.5 linkuse as main transcript	n.699+878C>G		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000212

AC:

AN:

1415384

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

701480

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:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.13e-7

Gnomad4 OTH exome

AF:

0.0000170

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

Jun 29, 2023

The c.929C>G (p.A310G) alteration is located in exon 3 (coding exon 1) of the ZNF497 gene. This alteration results from a C to G substitution at nucleotide position 929, causing the alanine (A) at amino acid position 310 to be replaced by a glycine (G). 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

0.091

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

4.9

DANN

Benign

0.83

DEOGEN2

Benign

0.045

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.14

.;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.085

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.029

Sift

Uncertain

0.019

D;D

Sift4G

Uncertain

0.040

D;D

Polyphen

0.17

B;B

Vest4

0.052

MutPred

0.50

Gain of helix (P = 0.132);Gain of helix (P = 0.132);

MVP

0.22

MPC

0.32

ClinPred

0.30

GERP RS

-2.2

Varity_R

0.14

gMVP

0.057

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