Genetic Variant ZNF292:p.Glu21Gln (chr6-87155652-G-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4

The NM_015021.3(ZNF292):c.61G>C(p.Glu21Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E21K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

ZNF292
NM_015021.3 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 4.70

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 6-87155652-G-C is Pathogenic according to our data. Variant chr6-87155652-G-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2576539.Status of the report is criteria_provided_single_submitter, 1 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.30353823). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF292	NM_015021.3 link	c.61G>C	p.Glu21Gln	missense_variant	Exon 1 of 8	ENST00000369577.8	NP_055836.1	O60281-1
ZNF292	NM_001351444.2 link	c.-505G>C		5_prime_UTR_variant	Exon 1 of 9		NP_001338373.1
ZNF292	XM_047418459.1 link	c.-673G>C		5_prime_UTR_variant	Exon 1 of 10		XP_047274415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF292	ENST00000369577.8 link	c.61G>C	p.Glu21Gln	missense_variant	Exon 1 of 8	1	NM_015021.3	ENSP00000358590.3		O60281-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Intellectual developmental disorder, autosomal dominant 64

Pathogenic:1

Aug 21, 2023

Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant has been identified by standard clinical testing. de novo Selected ACMG criteria: Likely pathogenic (II):BP1;PM2;PS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.076

T;T;T;T

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

T;T;T;T

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.30

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.6

.;L;.;.

PhyloP100

4.7

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.5

D;N;N;N

REVEL

Benign

0.039

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;T;D;T

Polyphen

0.97

.;D;.;.

Vest4

0.52

MutPred

0.22

Gain of MoRF binding (P = 0.0714);Gain of MoRF binding (P = 0.0714);Gain of MoRF binding (P = 0.0714);Gain of MoRF binding (P = 0.0714);

MVP

0.14

ClinPred

0.96

GERP RS

4.5

PromoterAI

-0.041

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.22

gMVP

0.35

Mutation Taster

=83/17

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over