chr1-212618229-C-G

Position:

• chr1-212618229-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001674.4(ATF3):​c.343C>G​(p.Gln115Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATF3 NM_001674.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.51

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATF3	NM_001674.4	c.343C>G	p.Gln115Glu	missense_variant	3/4	ENST00000341491.9	NP_001665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATF3	ENST00000341491.9	c.343C>G	p.Gln115Glu	missense_variant	3/4	1	NM_001674.4	ENSP00000344352.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 21, 2023

The c.343C>G (p.Q115E) alteration is located in exon 3 (coding exon 2) of the ATF3 gene. This alteration results from a C to G substitution at nucleotide position 343, causing the glutamine (Q) at amino acid position 115 to be replaced by a glutamic acid (E). 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	0.44
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T;.;T;.;.;.
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D;D;D;.;D;D;.
M_CAP	Pathogenic	0.38	D
MetaRNN	Uncertain	0.64	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Uncertain	2.6	.;M;.;M;.;M;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.1	N;N;.;N;N;N;.
REVEL	Benign	0.27
Sift	Benign	0.092	T;T;.;T;D;D;.
Sift4G	Benign	0.38	T;T;T;T;D;D;T
Polyphen		0.98	.;D;.;D;.;.;.
Vest4		0.65, 0.63, 0.68, 0.65
MutPred		0.42		Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);.;Loss of helix (P = 0.0237);.;Loss of helix (P = 0.0237);.;
MVP		0.88
MPC		1.4
ClinPred		0.75	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.28
gMVP		0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-212791571;