rs1864182

Variant names:

• chr5-82253421-C-A
• rs1864182
• NM_031482.5:c.659C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-82253421-C-A
• chr5-82253421-C-G
• chr5-82253421-C-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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142
• Publications: 54 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=9.702688E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031482.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG10	NM_031482.5	MANE Select	c.659C>A	p.Pro220His	missense	Exon 7 of 8	NP_113670.1	Q9H0Y0-1
	ATG10	NM_001131028.2		c.659C>A	p.Pro220His	missense	Exon 8 of 9	NP_001124500.1	Q9H0Y0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG10	ENST00000282185.8	TSL:1 MANE Select	c.659C>A	p.Pro220His	missense	Exon 7 of 8	ENSP00000282185.3	Q9H0Y0-1
	ATG10	ENST00000458350.7	TSL:1	c.659C>A	p.Pro220His	missense	Exon 8 of 9	ENSP00000404938.3	Q9H0Y0-1
	ATG10	ENST00000866604.1		c.659C>A	p.Pro220His	missense	Exon 8 of 9	ENSP00000536663.1

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

GnomAD2 exomes AF: 0.588 AC: 147628 AN: 250936 AF XY: 0.591

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

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

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

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

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 v4.9

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
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
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.14
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.45	N
REVEL	Benign	0.049
Sift	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.024
MPC		0.52
ClinPred		0.0090	T
GERP RS		-2.7
Varity_R		0.088
gMVP		0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1864182; hg19: chr5-81549240; COSMIC: COSV107280908; COSMIC: COSV107280908;