5-82253421-C-T

Variant names:

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

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>T​(p.Pro220Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• 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=0.04993829).

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>T	p.Pro220Leu	missense	Exon 7 of 8	NP_113670.1	Q9H0Y0-1
	ATG10	NM_001131028.2		c.659C>T	p.Pro220Leu	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>T	p.Pro220Leu	missense	Exon 7 of 8	ENSP00000282185.3	Q9H0Y0-1
	ATG10	ENST00000458350.7	TSL:1	c.659C>T	p.Pro220Leu	missense	Exon 8 of 9	ENSP00000404938.3	Q9H0Y0-1
	ATG10	ENST00000866604.1		c.659C>T	p.Pro220Leu	missense	Exon 8 of 9	ENSP00000536663.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.5
DANN	Benign	0.49
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.14
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.011
Sift	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.11
MutPred		0.31		Gain of helix (P = 0.0854)
MVP		0.061
MPC		0.39
ClinPred		0.093	T
GERP RS		-2.7
Varity_R		0.035
gMVP		0.44
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;