dbSNP rs3734114: ATG10:p.Ser62Pro (chr5-82058570-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_031482.5(ATG10):c.184T>C(p.Ser62Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,610,556 control chromosomes in the GnomAD database, including 34,675 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.17 ( 2506 hom., cov: 31)

Exomes 𝑓: 0.20 ( 32169 hom. )

Consequence

ATG10
NM_031482.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.770

Publications

33 publications found

Variant links:

Genes affected

ATG10 (HGNC:20315): (autophagy related 10) Autophagy is a process for the bulk degradation of cytosolic compartments by lysosomes. ATG10 is an E2-like enzyme involved in 2 ubiquitin-like modifications essential for autophagosome formation: ATG12 (MIM 609608)-ATG5 (MIM 604261) conjugation and modification of a soluble form of MAP-LC3 (MAP1LC3A; MIM 601242), a homolog of yeast Apg8, to a membrane-bound form (Nemoto et al., 2003 [PubMed 12890687]).[supplied by OMIM, Mar 2008]

ATG10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035431683).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG10	NM_031482.5 link	c.184T>C	p.Ser62Pro	missense_variant	Exon 3 of 8	ENST00000282185.8	NP_113670.1	Q9H0Y0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG10	ENST00000282185.8 link	c.184T>C	p.Ser62Pro	missense_variant	Exon 3 of 8	1	NM_031482.5	ENSP00000282185.3		Q9H0Y0-1

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25325

AN:

151892

Hom.:

2505

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0747

Gnomad AMI

AF:

0.160

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.185

Gnomad EAS

AF:

0.202

Gnomad SAS

AF:

0.361

Gnomad FIN

AF:

0.242

Gnomad MID

AF:

0.172

Gnomad NFE

AF:

0.199

Gnomad OTH

AF:

0.168

GnomAD2 exomes

AF:

0.206

AC:

51714

AN:

250878

AF XY:

0.219

show subpopulations

Gnomad AFR exome

AF:

0.0751

Gnomad AMR exome

AF:

0.129

Gnomad ASJ exome

AF:

0.181

Gnomad EAS exome

AF:

0.213

Gnomad FIN exome

AF:

0.240

Gnomad NFE exome

AF:

0.200

Gnomad OTH exome

AF:

0.196

GnomAD4 exome

AF:

0.202

AC:

295163

AN:

1458546

Hom.:

32169

Cov.:

AF XY:

0.209

AC XY:

151689

AN XY:

725650

show subpopulations

African (AFR)

AF:

0.0747

AC:

2495

AN:

33420

American (AMR)

AF:

0.131

AC:

5856

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

4870

AN:

26078

East Asian (EAS)

AF:

0.164

AC:

6506

AN:

39622

South Asian (SAS)

AF:

0.367

AC:

31493

AN:

85916

European-Finnish (FIN)

AF:

0.237

AC:

12651

AN:

53336

Middle Eastern (MID)

AF:

0.202

AC:

1166

AN:

5760

European-Non Finnish (NFE)

AF:

0.197

AC:

218247

AN:

1109494

Other (OTH)

AF:

0.197

AC:

11879

AN:

60242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

10713

21425

32138

42850

53563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7598

15196

22794

30392

37990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.167

AC:

25326

AN:

152010

Hom.:

2506

Cov.:

AF XY:

0.173

AC XY:

12869

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.0748

AC:

3103

AN:

41510

American (AMR)

AF:

0.143

AC:

2190

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.185

AC:

641

AN:

3464

East Asian (EAS)

AF:

0.202

AC:

1039

AN:

5150

South Asian (SAS)

AF:

0.362

AC:

1739

AN:

4808

European-Finnish (FIN)

AF:

0.242

AC:

2559

AN:

10578

Middle Eastern (MID)

AF:

0.175

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.199

AC:

13510

AN:

67922

Other (OTH)

AF:

0.165

AC:

348

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1022

2044

3067

4089

5111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

304

608

912

1216

1520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.188

Hom.:

9753

Bravo

AF:

0.151

TwinsUK

AF:

0.202

AC:

750

ALSPAC

AF:

0.210

AC:

811

ESP6500AA

AF:

0.0817

AC:

360

ESP6500EA

AF:

0.202

AC:

1736

ExAC

AF:

0.209

AC:

25394

Asia WGS

AF:

0.262

AC:

910

AN:

3476

EpiCase

AF:

0.200

EpiControl

AF:

0.200

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.3

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.031

.;T;T;.;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.51

.;.;T;T;T

MetaRNN

Benign

0.0035

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L;L;L;.

PhyloP100

0.77

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.55

N;N;N;N;N

REVEL

Benign

0.028

Sift

Benign

0.29

T;T;T;T;T

Sift4G

Benign

0.16

T;T;T;T;T

Polyphen

0.089

B;B;B;B;.

Vest4

0.17

MPC

0.14

ClinPred

0.0013

GERP RS

0.71

Varity_R

0.15

gMVP

0.24

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over