Genetic Variant E2F3:p.Ala8Thr (chr6-20402254-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001949.5(E2F3):c.22G>A(p.Ala8Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A8S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

E2F3
NM_001949.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.50

Publications

0 publications found

Variant links:

Genes affected

E2F3 (HGNC:3115): (E2F transcription factor 3) This gene encodes a member of a small family of transcription factors that function through binding of DP interaction partner proteins. The encoded protein recognizes a specific sequence motif in DNA and interacts directly with the retinoblastoma protein (pRB) to regulate the expression of genes involved in the cell cycle. Altered copy number and activity of this gene have been observed in a number of human cancers. There are pseudogenes for this gene on chromosomes 2 and 17. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

E2F3 links:

LOC124901482 (HGNC:):

LOC124901482 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2937399).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001949.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F3	NM_001949.5	MANE Select	c.22G>A	p.Ala8Thr	missense	Exon 1 of 7	NP_001940.1	O00716-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
E2F3	ENST00000346618.8	TSL:1 MANE Select	c.22G>A	p.Ala8Thr	missense	Exon 1 of 7	ENSP00000262904.4	O00716-1
E2F3	ENST00000938961.1		c.22G>A	p.Ala8Thr	missense	Exon 1 of 7	ENSP00000609020.1
ENSG00000289981	ENST00000702275.2		n.73-92C>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1447308

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720276

African (AFR)

AF:

0.00

AC:

AN:

32180

American (AMR)

AF:

0.00

AC:

AN:

40066

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25348

East Asian (EAS)

AF:

0.00

AC:

AN:

39262

South Asian (SAS)

AF:

0.00

AC:

AN:

84454

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5520

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108438

Other (OTH)

AF:

0.00

AC:

AN:

59742

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.56

M_CAP

Benign

0.010

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.0

PhyloP100

4.5

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.52

REVEL

Benign

0.078

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.034

Polyphen

0.84

Vest4

0.50

MutPred

0.30

Loss of helix (P = 0.0104)

MVP

0.24

MPC

1.1

ClinPred

0.71

GERP RS

4.3

PromoterAI

-0.043

Neutral

(source)

Varity_R

0.31

gMVP

0.80

Mutation Taster

=80/20

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over