rs1864183

Variant names:

• chr5-82253397-C-T
• rs1864183
• NM_031482.5:c.635C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031482.5(ATG10):​c.635C>T​(p.Thr212Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 1,600,552 control chromosomes in the GnomAD database, including 186,484 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 0.41 (15150 hom., cov: 32)
  • Exomes 𝑓: 0.47 (171334 hom.)
• Consequence: ATG10 NM_031482.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820
• Publications: 75 publications found

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

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

• BP4: Computational evidence support a benign effect (MetaRNN=8.61997E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG10	NM_031482.5	c.635C>T	p.Thr212Met	missense_variant	Exon 7 of 8	ENST00000282185.8	NP_113670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG10	ENST00000282185.8	c.635C>T	p.Thr212Met	missense_variant	Exon 7 of 8	1	NM_031482.5	ENSP00000282185.3

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63036 AN: 151956 Hom.: 15130 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.422

GnomAD2 exomes AF: 0.519 AC: 130333 AN: 251262 AF XY: 0.518

Gnomad AFR exome AF: 0.189

Gnomad AMR exome AF: 0.680

Gnomad ASJ exome AF: 0.390

Gnomad EAS exome AF: 0.884

Gnomad FIN exome AF: 0.482

Gnomad NFE exome AF: 0.459

Gnomad OTH exome AF: 0.485

GnomAD4 exome AF: 0.474 AC: 686491 AN: 1448478 Hom.: 171334 Cov.: 32 AF XY: 0.478 AC XY: 345136 AN XY: 721396

African (AFR) AF: 0.186 AC: 6193 AN: 33320

American (AMR) AF: 0.664 AC: 29660 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 10309 AN: 26052

East Asian (EAS) AF: 0.916 AC: 36296 AN: 39628

South Asian (SAS) AF: 0.583 AC: 50139 AN: 85962

European-Finnish (FIN) AF: 0.486 AC: 25945 AN: 53404

Middle Eastern (MID) AF: 0.445 AC: 2556 AN: 5738

European-Non Finnish (NFE) AF: 0.452 AC: 497580 AN: 1099710

Other (OTH) AF: 0.464 AC: 27813 AN: 59970

GnomAD4 genome AF: 0.415 AC: 63068 AN: 152074 Hom.: 15150 Cov.: 32 AF XY: 0.423 AC XY: 31459 AN XY: 74320

African (AFR) AF: 0.196 AC: 8114 AN: 41488

American (AMR) AF: 0.550 AC: 8400 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1363 AN: 3466

East Asian (EAS) AF: 0.888 AC: 4590 AN: 5170

South Asian (SAS) AF: 0.601 AC: 2907 AN: 4834

European-Finnish (FIN) AF: 0.481 AC: 5071 AN: 10542

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31335 AN: 67978

Other (OTH) AF: 0.428 AC: 903 AN: 2112

Alfa AF: 0.441 Hom.: 41214

Bravo AF: 0.410

TwinsUK AF: 0.461 AC: 1709

ALSPAC AF: 0.445 AC: 1716

ESP6500AA AF: 0.207 AC: 913

ESP6500EA AF: 0.465 AC: 3996

ExAC AF: 0.509 AC: 61821

Asia WGS AF: 0.715 AC: 2487 AN: 3478

EpiCase AF: 0.459

EpiControl AF: 0.454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.90
DEOGEN2	Benign	0.014	T;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.59	.;T
MetaRNN	Benign	8.6e-7	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PhyloP100		-0.082
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.15	N;N
REVEL	Benign	0.072
Sift	Benign	0.14	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.11	B;B
Vest4		0.041
MPC		0.12
ClinPred		0.0069	T
GERP RS		1.6
Varity_R		0.027
gMVP		0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1864183; hg19: chr5-81549216; COSMIC: COSV56424284; COSMIC: COSV56424284;