dbSNP rs1864182: ATG10:p.Pro220His (chr5-82253421-C-A) – 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.659C>A(p.Pro220His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,558,954 control chromosomes in the GnomAD database, including 246,004 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P220A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.48 ( 19865 hom., cov: 33)

Exomes 𝑓: 0.56 ( 226139 hom. )

Consequence

ATG10
NM_031482.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.142

Publications

54 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=9.702688E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG10	NM_031482.5 link	c.659C>A	p.Pro220His	missense_variant	Exon 7 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.659C>A	p.Pro220His	missense_variant	Exon 7 of 8	1	NM_031482.5	ENSP00000282185.3		Q9H0Y0-1

Frequencies

GnomAD3 genomes

AF:

0.477

AC:

72535

AN:

152042

Hom.:

19844

Cov.:

show subpopulations

Gnomad AFR

AF:

0.213

Gnomad AMI

AF:

0.373

Gnomad AMR

AF:

0.591

Gnomad ASJ

AF:

0.470

Gnomad EAS

AF:

0.912

Gnomad SAS

AF:

0.683

Gnomad FIN

AF:

0.585

Gnomad MID

AF:

0.433

Gnomad NFE

AF:

0.549

Gnomad OTH

AF:

0.478

GnomAD2 exomes

AF:

0.588

AC:

147628

AN:

250936

AF XY:

0.591

show subpopulations

Gnomad AFR exome

AF:

0.203

Gnomad AMR exome

AF:

0.708

Gnomad ASJ exome

AF:

0.463

Gnomad EAS exome

AF:

0.908

Gnomad FIN exome

AF:

0.588

Gnomad NFE exome

AF:

0.547

Gnomad OTH exome

AF:

0.553

GnomAD4 exome

AF:

0.557

AC:

783417

AN:

1406794

Hom.:

226139

Cov.:

AF XY:

0.561

AC XY:

394604

AN XY:

702850

show subpopulations

African (AFR)

AF:

0.196

AC:

6414

AN:

32696

American (AMR)

AF:

0.695

AC:

30957

AN:

44568

Ashkenazi Jewish (ASJ)

AF:

0.464

AC:

11957

AN:

25790

East Asian (EAS)

AF:

0.941

AC:

36990

AN:

39322

South Asian (SAS)

AF:

0.663

AC:

56311

AN:

84936

European-Finnish (FIN)

AF:

0.590

AC:

31476

AN:

53372

Middle Eastern (MID)

AF:

0.494

AC:

2794

AN:

5652

European-Non Finnish (NFE)

AF:

0.541

AC:

574907

AN:

1061888

Other (OTH)

AF:

0.540

AC:

31611

AN:

58570

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

15009

30019

45028

60038

75047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15952

31904

47856

63808

79760

<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:

0.477

AC:

72567

AN:

152160

Hom.:

19865

Cov.:

AF XY:

0.486

AC XY:

36125

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.213

AC:

8837

AN:

41534

American (AMR)

AF:

0.592

AC:

9044

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.470

AC:

1628

AN:

3464

East Asian (EAS)

AF:

0.912

AC:

4720

AN:

5176

South Asian (SAS)

AF:

0.682

AC:

3296

AN:

4830

European-Finnish (FIN)

AF:

0.585

AC:

6193

AN:

10578

Middle Eastern (MID)

AF:

0.445

AC:

130

AN:

292

European-Non Finnish (NFE)

AF:

0.550

AC:

37354

AN:

67978

Other (OTH)

AF:

0.485

AC:

1025

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1733

3466

5200

6933

8666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

652

1304

1956

2608

3260

<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:

0.535

Hom.:

79847

Bravo

AF:

0.464

TwinsUK

AF:

0.562

AC:

2084

ALSPAC

AF:

0.536

AC:

2065

ESP6500AA

AF:

0.224

AC:

986

ESP6500EA

AF:

0.559

AC:

4809

ExAC

AF:

0.579

AC:

70259

Asia WGS

AF:

0.760

AC:

2643

AN:

3478

EpiCase

AF:

0.542

EpiControl

AF:

0.539

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

5.2

(source)

DANN

Benign

0.47

DEOGEN2

Benign

0.014

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00032

LIST_S2

Benign

0.16

.;T

MetaRNN

Benign

9.7e-7

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

N;N

PhyloP100

-0.14

PrimateAI

Benign

0.32

PROVEAN

Benign

0.45

N;N

REVEL

Benign

0.049

Sift

Pathogenic

0.0

D;D

Polyphen

0.0

B;B

Vest4

0.024

MPC

0.52

ClinPred

0.0090

GERP RS

-2.7

Varity_R

0.088

gMVP

0.43

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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