Variant chr11-46668863-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001346311.2(ATG13):c.1399G>A(p.Gly467Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00884 in 1,613,856 control chromosomes in the GnomAD database, including 137 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0074 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0090 ( 126 hom. )

Consequence

ATG13
NM_001346311.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.33

Variant links:

Genes affected

ATG13 (HGNC:29091): (autophagy related 13) The protein encoded by this gene is an autophagy factor and a target of the TOR kinase signaling pathway. The encoded protein is essential for autophagosome formation and mitophagy. [provided by RefSeq, Oct 2016]

ATG13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004194081).

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00736 (1120/152226) while in subpopulation SAS AF= 0.0228 (110/4816). AF 95% confidence interval is 0.0194. There are 11 homozygotes in gnomad4. There are 653 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG13	NM_001346311.2 link	c.1399G>A	p.Gly467Arg	missense_variant	17/19	ENST00000683050.1	NP_001333240.1	O75143-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG13	ENST00000683050.1 link	c.1399G>A	p.Gly467Arg	missense_variant	17/19		NM_001346311.2	ENSP00000507809.1		O75143-5

Frequencies

GnomAD3 genomes

AF:

0.00738

AC:

1122

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0232

Gnomad FIN

AF:

0.0295

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00823

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.0106

AC:

2655

AN:

250934

Hom.:

AF XY:

0.0114

AC XY:

1553

AN XY:

135700

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00185

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0228

Gnomad FIN exome

AF:

0.0291

Gnomad NFE exome

AF:

0.0103

Gnomad OTH exome

AF:

0.00832

GnomAD4 exome

AF:

0.00900

AC:

13151

AN:

1461630

Hom.:

126

Cov.:

AF XY:

0.00946

AC XY:

6881

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.00174

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0214

Gnomad4 FIN exome

AF:

0.0278

Gnomad4 NFE exome

AF:

0.00831

Gnomad4 OTH exome

AF:

0.00682

GnomAD4 genome

AF:

0.00736

AC:

1120

AN:

152226

Hom.:

Cov.:

AF XY:

0.00878

AC XY:

653

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.00130

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0228

Gnomad4 FIN

AF:

0.0295

Gnomad4 NFE

AF:

0.00823

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00710

Hom.:

Bravo

AF:

0.00468

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00779

AC:

ExAC

AF:

0.0109

AC:

1320

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.00742

EpiControl

AF:

0.00711

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

.;.;T;.;T;.;T

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.019

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.74

.;T;.;T;T;T;T

MetaRNN

Benign

0.0042

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

.;.;N;.;N;.;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.060

N;N;N;N;N;N;D

REVEL

Benign

0.026

Sift

Benign

0.71

T;T;T;T;T;T;T

Sift4G

Benign

0.91

T;T;T;T;T;T;D

Polyphen

0.13

B;.;B;B;B;.;.

Vest4

0.23

MutPred

0.40

.;.;Loss of glycosylation at S433 (P = 0.0733);.;Loss of glycosylation at S433 (P = 0.0733);.;.;

MPC

0.47

ClinPred

0.048

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.033

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over