Variant chr6-20402254-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001949.5(E2F3):c.22G>T(p.Ala8Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000229 in 1,599,338 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 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

E2F3
NM_001949.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.50

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14109722).

BS2

High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
E2F3	NM_001949.5 linkuse as main transcript	c.22G>T	p.Ala8Ser	missense_variant	1/7	ENST00000346618.8	NP_001940.1
LOC124901482	XM_047419652.1 linkuse as main transcript	c.460+15C>A		intron_variant			XP_047275608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
E2F3	ENST00000346618.8 linkuse as main transcript	c.22G>T	p.Ala8Ser	missense_variant	1/7	1	NM_001949.5	ENSP00000262904		O00716-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

151912

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000112

AC:

AN:

232424

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

127736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000473

Gnomad NFE exome

AF:

0.000225

Gnomad OTH exome

AF:

0.000179

GnomAD4 exome

AF:

0.000243

AC:

351

AN:

1447308

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

175

AN XY:

720276

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000499

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000382

Gnomad4 NFE exome

AF:

0.000307

Gnomad4 OTH exome

AF:

0.000117

GnomAD4 genome

AF:

0.000105

AC:

AN:

152030

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000185

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000235

AC:

ExAC

AF:

0.000132

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Dec 21, 2022

The c.22G>T (p.A8S) alteration is located in exon 1 (coding exon 1) of the E2F3 gene. This alteration results from a G to T substitution at nucleotide position 22, causing the alanine (A) at amino acid position 8 to be replaced by a serine (S). 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

0.11

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

Eigen

Benign

-0.052

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.51

M_CAP

Benign

0.0081

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.53

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.40

REVEL

Benign

0.087

Sift

Pathogenic

0.0

Sift4G

Benign

0.095

Polyphen

0.33

Vest4

0.42

MVP

0.26

MPC

1.1

ClinPred

0.23

GERP RS

4.3

Varity_R

0.28

gMVP

0.72

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