Variant 3-112534296-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_022488.5(ATG3):c.836A>C(p.Glu279Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000211 in 1,599,138 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 0.000093 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

ATG3
NM_022488.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.64

Variant links:

Genes affected

ATG3 (HGNC:20962): (autophagy related 3) This gene encodes a ubiquitin-like-conjugating enzyme and is a component of ubiquitination-like systems involved in autophagy, the process of degradation, turnover and recycling of cytoplasmic constituents in eukaryotic cells. This protein is known to play a role in regulation of autophagy during cell death. A pseudogene of this gene is located on chromosome 20. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

ATG3 links:

ATG3 (HGNC:):

ATG3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.41883862).

BS2

High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG3	NM_022488.5 linkuse as main transcript	c.836A>C	p.Glu279Ala	missense_variant	11/12	ENST00000283290.10	NP_071933.2	Q9NT62-1
ATG3	NM_001278712.2 linkuse as main transcript	c.836A>C	p.Glu279Ala	missense_variant	11/11		NP_001265641.1	Q9NT62-2
ATG3	XM_011513074.1 linkuse as main transcript	c.575A>C	p.Glu192Ala	missense_variant	11/12		XP_011511376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ATG3	ENST00000283290.10 linkuse as main transcript	c.836A>C	p.Glu279Ala	missense_variant	11/12	1	NM_022488.5	ENSP00000283290.5	Q9NT62-1
ATG3	ENST00000402314.6 linkuse as main transcript	c.836A>C	p.Glu279Ala	missense_variant	11/11	1		ENSP00000385943.2	Q9NT62-2
ATG3	ENST00000494571.1 linkuse as main transcript	n.2472A>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000928

AC:

AN:

150820

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000177

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000664

AC:

AN:

240960

Hom.:

AF XY:

0.0000536

AC XY:

AN XY:

130600

show subpopulations

Gnomad AFR exome

AF:

0.0000631

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:

0.0000471

Gnomad NFE exome

AF:

0.000127

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000223

AC:

323

AN:

1448318

Hom.:

Cov.:

AF XY:

0.000186

AC XY:

134

AN XY:

720588

show subpopulations

Gnomad4 AFR exome

AF:

0.0000608

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:

0.0000757

Gnomad4 NFE exome

AF:

0.000279

Gnomad4 OTH exome

AF:

0.000151

GnomAD4 genome

AF:

0.0000928

AC:

AN:

150820

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

73468

show subpopulations

Gnomad4 AFR

AF:

0.0000486

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000141

Hom.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000247

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

Feb 16, 2023

The c.836A>C (p.E279A) alteration is located in exon 11 (coding exon 11) of the ATG3 gene. This alteration results from a A to C substitution at nucleotide position 836, causing the glutamic acid (E) at amino acid position 279 to be replaced by an alanine (A). 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

Pathogenic

0.83

BayesDel_addAF

Uncertain

0.016

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

T;.

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.42

T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

2.0

M;M

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-5.0

D;D

REVEL

Benign

0.28

Sift

Benign

0.081

T;D

Sift4G

Benign

0.11

T;T

Polyphen

0.86

P;P

Vest4

0.63

MVP

0.57

MPC

1.4

ClinPred

0.46

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.47

gMVP

0.66

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