5-82253421-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031482.5(ATG10):​c.659C>G​(p.Pro220Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,417,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04505244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG10	NM_031482.5	c.659C>G	p.Pro220Arg	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.659C>G	p.Pro220Arg	missense_variant	Exon 7 of 8	1	NM_031482.5	ENSP00000282185.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1417672 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 707816

African (AFR) AF: 0.00 AC: 0 AN: 32810

American (AMR) AF: 0.0000448 AC: 2 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25886

East Asian (EAS) AF: 0.00 AC: 0 AN: 39344

South Asian (SAS) AF: 0.00 AC: 0 AN: 85180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1071830

Other (OTH) AF: 0.00 AC: 0 AN: 58918

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 79847

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.6
DANN	Benign	0.28
DEOGEN2	Benign	0.014	T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.20	.;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.045	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PhyloP100		-0.14
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.13	N;N
REVEL	Benign	0.013
Sift	Pathogenic	0.0	D;D
Polyphen		0.0	B;B
Vest4		0.056
MutPred		0.27		Gain of solvent accessibility (P = 0.0216);Gain of solvent accessibility (P = 0.0216);
MVP		0.055
MPC		0.45
ClinPred		0.070	T
GERP RS		-2.7
Varity_R		0.059
gMVP		0.45
Mutation Taster		=100/0	polymorphism

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;