chr5-82253421-C-A

Position:

• chr5-82253421-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000282185.8(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. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. 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 ENST00000282185.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ATG10	NM_031482.5	c.659C>A	p.Pro220His	missense_variant	7/8	ENST00000282185.8	NP_113670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG10	ENST00000282185.8	c.659C>A	p.Pro220His	missense_variant	7/8	1	NM_031482.5	ENSP00000282185	P1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72535 AN: 152042 Hom.: 19844 Cov.: 33

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

GnomAD3 exomes AF: 0.588 AC: 147628 AN: 250936 Hom.: 46420 AF XY: 0.591 AC XY: 80095 AN XY: 135606

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 SAS exome AF: 0.667

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.: 28 AF XY: 0.561 AC XY: 394604 AN XY: 702850

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.695

Gnomad4 ASJ exome AF: 0.464

Gnomad4 EAS exome AF: 0.941

Gnomad4 SAS exome AF: 0.663

Gnomad4 FIN exome AF: 0.590

Gnomad4 NFE exome AF: 0.541

Gnomad4 OTH exome AF: 0.540

GnomAD4 genome AF: 0.477 AC: 72567 AN: 152160 Hom.: 19865 Cov.: 33 AF XY: 0.486 AC XY: 36125 AN XY: 74398

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.912

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.485

Alfa AF: 0.540 Hom.: 56385

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	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.2
DANN	Benign	0.47
DEOGEN2	Benign	0.014	T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00032	N
LIST_S2	Benign	0.16	.;T
MetaRNN	Benign	9.7e-7	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.32	T
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	T
GERP RS		-2.7
Varity_R		0.088
gMVP		0.43

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

Other links and lift over

dbSNP: rs1864182; hg19: chr5-81549240;