Variant chr19-49932611-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001193646.2(ATF5):c.368C>G(p.Pro123Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 19)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ATF5
NM_001193646.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.55

Variant links:

Genes affected

ATF5 (HGNC:790): (activating transcription factor 5) Enables several functions, including DNA-binding transcription activator activity, RNA polymerase II-specific; RNA polymerase II transcription regulatory region sequence-specific DNA binding activity; and tubulin binding activity. Involved in several processes, including fat cell differentiation; regulation of cell cycle process; and regulation of transcription, DNA-templated. Located in centrosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ATF5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ATF5	NM_001193646.2 linkuse as main transcript	c.368C>G	p.Pro123Arg	missense_variant	3/3	ENST00000423777.7	NP_001180575.1
ATF5	NM_001290746.2 linkuse as main transcript	c.368C>G	p.Pro123Arg	missense_variant	3/3		NP_001277675.1
ATF5	NM_012068.6 linkuse as main transcript	c.368C>G	p.Pro123Arg	missense_variant	4/4		NP_036200.2
ATF5	XM_011526629.4 linkuse as main transcript	c.368C>G	p.Pro123Arg	missense_variant	3/3		XP_011524931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ATF5	ENST00000423777.7 linkuse as main transcript	c.368C>G	p.Pro123Arg	missense_variant	3/3	1	NM_001193646.2	ENSP00000396954	P1
ATF5	ENST00000595125.5 linkuse as main transcript	c.368C>G	p.Pro123Arg	missense_variant	4/4	2		ENSP00000470633	P1
ATF5	ENST00000596658.1 linkuse as main transcript	c.368C>G	p.Pro123Arg	missense_variant	3/3	2		ENSP00000470464
ATF5	ENST00000597227.5 linkuse as main transcript			downstream_gene_variant		3		ENSP00000470978

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1404828

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

693982

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 13, 2024

The c.368C>G (p.P123R) alteration is located in exon 4 (coding exon 2) of the ATF5 gene. This alteration results from a C to G substitution at nucleotide position 368, causing the proline (P) at amino acid position 123 to be replaced by an arginine (R). 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

0.20

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.052

T;T;.

Eigen

Benign

-0.059

Eigen_PC

Benign

-0.070

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.46

.;T;T

M_CAP

Uncertain

0.23

MetaRNN

Uncertain

0.63

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L;.

MutationTaster

Benign

0.99

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.3

.;N;.

REVEL

Benign

0.12

Sift

Benign

0.044

.;D;.

Sift4G

Uncertain

0.0090

D;D;T

Polyphen

0.84

P;P;.

Vest4

0.29

MutPred

0.48

Loss of glycosylation at P123 (P = 0.0048);Loss of glycosylation at P123 (P = 0.0048);Loss of glycosylation at P123 (P = 0.0048);

MVP

0.64

MPC

0.063

ClinPred

0.47

GERP RS

3.7

Varity_R

0.040

gMVP

0.38

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over