12-50814319-C-T

Position:

chr12-50814319-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005171.5(ATF1):c.551C>T(p.Thr184Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,614,230 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ATF1
NM_005171.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.60

Variant links:

Genes affected

ATF1 (HGNC:783): (activating transcription factor 1) This gene encodes an activating transcription factor, which belongs to the ATF subfamily and bZIP (basic-region leucine zipper) family. It influences cellular physiologic processes by regulating the expression of downstream target genes, which are related to growth, survival, and other cellular activities. This protein is phosphorylated at serine 63 in its kinase-inducible domain by serine/threonine kinases, cAMP-dependent protein kinase A, calmodulin-dependent protein kinase I/II, mitogen- and stress-activated protein kinase and cyclin-dependent kinase 3 (cdk-3). Its phosphorylation enhances its transactivation and transcriptional activities, and enhances cell transformation. Fusion of this gene and FUS on chromosome 16 or EWSR1 on chromosome 22 induced by translocation generates chimeric proteins in angiomatoid fibrous histiocytoma and clear cell sarcoma. This gene has a pseudogene on chromosome 6. [provided by RefSeq, Aug 2010]

ATF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22208151).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATF1	NM_005171.5 link	c.551C>T	p.Thr184Ile	missense_variant	6/7	ENST00000262053.8	NP_005162.1	P18846-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ATF1	ENST00000262053.8 link	c.551C>T	p.Thr184Ile	missense_variant	6/7	1	NM_005171.5	ENSP00000262053.3	P18846-1
ATF1	ENST00000552487.1 link	c.551C>T	p.Thr184Ile	missense_variant	6/6	5		ENSP00000448921.1	F8VYN3
ATF1	ENST00000551831.5 link	n.*148C>T		non_coding_transcript_exon_variant	5/6	2		ENSP00000448987.1	F8VYE5
ATF1	ENST00000551831.5 link	n.*148C>T		3_prime_UTR_variant	5/6	2		ENSP00000448987.1	F8VYE5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251390

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Feb 06, 2024

The c.551C>T (p.T184I) alteration is located in exon 6 (coding exon 5) of the ATF1 gene. This alteration results from a C to T substitution at nucleotide position 551, causing the threonine (T) at amino acid position 184 to be replaced by an isoleucine (I). 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

0.29

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

D;D

M_CAP

Benign

0.034

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.1

M;.

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.10

Sift

Uncertain

0.0040

D;D

Sift4G

Benign

0.074

T;D

Polyphen

0.92

P;.

Vest4

0.48

MutPred

0.33

Loss of glycosylation at T184 (P = 0.0069);Loss of glycosylation at T184 (P = 0.0069);

MVP

0.27

MPC

0.81

ClinPred

0.82

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.23

gMVP

0.67

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