Variant 1-119623597-C-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_001080470.2(ZNF697):c.746G>C(p.Gly249Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000279 in 1,433,388 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: 0.0000016 ( 0 hom. )

Consequence

ZNF697
NM_001080470.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.138

Variant links:

Genes affected

ZNF697 (HGNC:32034): (zinc finger protein 697) 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 by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF697 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=0.08698818).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF697	NM_001080470.2 linkuse as main transcript	c.746G>C	p.Gly249Ala	missense_variant	3/3	ENST00000421812.3	NP_001073939.1
ZNF697	XM_005271315.4 linkuse as main transcript	c.746G>C	p.Gly249Ala	missense_variant	3/3		XP_005271372.1
ZNF697	XM_047433849.1 linkuse as main transcript	c.746G>C	p.Gly249Ala	missense_variant	4/4		XP_047289805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF697	ENST00000421812.3 linkuse as main transcript	c.746G>C	p.Gly249Ala	missense_variant	3/3	3	NM_001080470.2	ENSP00000396857	P1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151606

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000156

AC:

AN:

1281782

Hom.:

Cov.:

AF XY:

0.00000159

AC XY:

AN XY:

627782

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000324

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000189

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151606

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74038

show subpopulations

Gnomad4 AFR

AF:

0.0000484

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

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

Sep 14, 2022

The c.746G>C (p.G249A) alteration is located in exon 3 (coding exon 2) of the ZNF697 gene. This alteration results from a G to C substitution at nucleotide position 746, causing the glycine (G) at amino acid position 249 to be replaced by an alanine (A). 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

0.086

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.24

M_CAP

Benign

0.080

MetaRNN

Benign

0.087

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.55

MutationTaster

Benign

0.96

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.35

REVEL

Benign

0.085

Sift

Benign

0.24

Sift4G

Benign

0.26

Polyphen

0.15

Vest4

0.10

MutPred

0.17

Loss of catalytic residue at G249 (P = 0.1094);

MVP

0.085

MPC

0.65

ClinPred

0.18

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

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