Genetic Variant ZNF292:p.Arg40Trp (chr6-87155709-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015021.3(ZNF292):c.118C>T(p.Arg40Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZNF292
NM_015021.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.525

Publications

0 publications found

Variant links:

Genes affected

ZNF292 (HGNC:18410): (zinc finger protein 292) This gene encodes a growth hormone-dependent, zinc finger transcription factor that functions as a tumor suppressor. Naturally occurring mutations in this gene are associated with gastric cancer, colorectal cancer, and chronic lymphocytic leukemia. [provided by RefSeq, May 2017]

ZNF292 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics, ClinGen
intellectual developmental disorder, autosomal dominant 64
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ZNF292 links:

ENSG00000272008 (HGNC:):

ENSG00000272008 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14406875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF292	NM_015021.3 link	c.118C>T	p.Arg40Trp	missense_variant	Exon 1 of 8	ENST00000369577.8	NP_055836.1	O60281-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF292	ENST00000369577.8 link	c.118C>T	p.Arg40Trp	missense_variant	Exon 1 of 8	1	NM_015021.3	ENSP00000358590.3		O60281-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1444612

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717012

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33194

American (AMR)

AF:

0.00

AC:

AN:

42718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25692

East Asian (EAS)

AF:

0.00

AC:

AN:

39092

South Asian (SAS)

AF:

0.00

AC:

AN:

83574

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51010

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4222

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1105514

Other (OTH)

AF:

0.00

AC:

AN:

59596

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Aug 08, 2019

GeneDx

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (Richards et al., 2015) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0058

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.33

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.89

PhyloP100

0.53

PROVEAN

Benign

1.6

REVEL

Benign

0.058

Sift

Pathogenic

0.0

MutPred

0.15

Loss of loop (P = 0.0203);

MVP

0.093

ClinPred

0.96

GERP RS

3.6

PromoterAI

-0.0037

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.11

Mutation Taster

=81/19

polymorphism

(source)

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

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6-87155709-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over