Variant 1-212615115-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000341491.9(ATF3):c.94G>A(p.Glu32Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ATF3
ENST00000341491.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.70

Variant links:

Genes affected

ATF3 (HGNC:785): (activating transcription factor 3) This gene encodes a member of the mammalian activation transcription factor/cAMP responsive element-binding (CREB) protein family of transcription factors. This gene is induced by a variety of signals, including many of those encountered by cancer cells, and is involved in the complex process of cellular stress response. Multiple transcript variants encoding different isoforms have been found for this gene. It is possible that alternative splicing of this gene may be physiologically important in the regulation of target genes. [provided by RefSeq, Apr 2011]

ATF3 links:

ATF3 (HGNC:):

ATF3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATF3	NM_001674.4 linkuse as main transcript	c.94G>A	p.Glu32Lys	missense_variant	2/4	ENST00000341491.9	NP_001665.1	P18847-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATF3	ENST00000341491.9 linkuse as main transcript	c.94G>A	p.Glu32Lys	missense_variant	2/4	1	NM_001674.4	ENSP00000344352.4		P18847-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000629

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00000824

AC:

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 22, 2023

The c.94G>A (p.E32K) alteration is located in exon 2 (coding exon 1) of the ATF3 gene. This alteration results from a G to A substitution at nucleotide position 94, causing the glutamic acid (E) at amino acid position 32 to be replaced by a lysine (K). 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

Uncertain

0.42

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T;T;.

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D;.;D

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.46

T;T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.2

.;L;L;L

MutationTaster

Benign

1.0

D;D;D;D;D

PROVEAN

Benign

-0.97

N;N;N;N

REVEL

Benign

0.26

Sift

Benign

0.046

D;T;T;D

Sift4G

Benign

0.52

T;T;T;T

Polyphen

0.46

.;P;P;.

Vest4

0.56, 0.38

MVP

0.78

MPC

0.030

ClinPred

0.51

GERP RS

6.1

BranchPoint Hunter

0.0

Varity_R

0.21

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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