Variant 19-58356201-A-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 NM_198458.3(ZNF497):c.1435T>C(p.Phe479Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000295 in 1,599,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

ZNF497
NM_198458.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.17

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:

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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=0.17860144).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF497	NM_198458.3 linkuse as main transcript	c.1435T>C	p.Phe479Leu	missense_variant	3/3	ENST00000311044.8	NP_940860.2	Q6ZNH5
ZNF497	NM_001207009.2 linkuse as main transcript	c.1435T>C	p.Phe479Leu	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.1435T>C	p.Phe479Leu	missense_variant	3/3	2	NM_198458.3	ENSP00000311183.2	Q6ZNH5
ZNF497	ENST00000425453.3 linkuse as main transcript	c.1435T>C	p.Phe479Leu	missense_variant	2/2	1		ENSP00000402815.2	Q6ZNH5
ENSG00000268230	ENST00000600123.5 linkuse as main transcript	n.25T>C		non_coding_transcript_exon_variant	1/8	1
ENSG00000268230	ENST00000599109.5 linkuse as main transcript	n.699+1384T>C		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000382

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000280

AC:

AN:

235376

Hom.:

AF XY:

0.000349

AC XY:

AN XY:

129072

show subpopulations

Gnomad AFR exome

AF:

0.000201

Gnomad AMR exome

AF:

0.000327

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:

0.000500

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000307

AC:

444

AN:

1446880

Hom.:

Cov.:

AF XY:

0.000316

AC XY:

227

AN XY:

717810

show subpopulations

Gnomad4 AFR exome

AF:

0.0000906

Gnomad4 AMR exome

AF:

0.000364

Gnomad4 ASJ exome

AF:

0.0000388

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000361

Gnomad4 OTH exome

AF:

0.000386

GnomAD4 genome

AF:

0.000177

AC:

AN:

152358

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000356

Hom.:

Bravo

AF:

0.000212

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000584

AC:

ExAC

AF:

0.000232

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

Nov 07, 2022

The c.1435T>C (p.F479L) alteration is located in exon 3 (coding exon 1) of the ZNF497 gene. This alteration results from a T to C substitution at nucleotide position 1435, causing the phenylalanine (F) at amino acid position 479 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

Pathogenic

1.0

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.068

T;T

Eigen

Benign

0.040

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.84

.;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

0.88

N;N

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-5.2

D;D

REVEL

Benign

0.12

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;D

Vest4

0.38

MutPred

0.72

Gain of MoRF binding (P = 0.1046);Gain of MoRF binding (P = 0.1046);

MVP

0.70

MPC

1.1

ClinPred

0.83

GERP RS

1.2

Varity_R

0.57

gMVP

0.15

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