chr5-82058508-G-T

Variant names:

• chr5-82058508-G-T
• rs564856686
• NM_031482.5:c.122G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031482.5(ATG10):​c.122G>T​(p.Gly41Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,156 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ATG10 NM_031482.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.47

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG10	NM_031482.5	c.122G>T	p.Gly41Val	missense_variant	Exon 3 of 8	ENST00000282185.8	NP_113670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG10	ENST00000282185.8	c.122G>T	p.Gly41Val	missense_variant	Exon 3 of 8	1	NM_031482.5	ENSP00000282185.3

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152038 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 250990 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135650

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152156 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74396

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	.;T;T;.;T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.83	.;.;T;T;T
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.53	D;D;D;D;D
MetaSVM	Benign	-0.36	T
MutationAssessor	Uncertain	2.5	M;M;M;M;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.0	N;D;D;N;D
REVEL	Benign	0.20
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Benign	0.12	T;D;D;T;D
Polyphen		1.0	D;D;D;D;.
Vest4		0.79
MutPred		0.49		Loss of ubiquitination at K36 (P = 0.0419);Loss of ubiquitination at K36 (P = 0.0419);Loss of ubiquitination at K36 (P = 0.0419);Loss of ubiquitination at K36 (P = 0.0419);Loss of ubiquitination at K36 (P = 0.0419);
MVP		0.84
MPC		0.60
ClinPred		0.92	D
GERP RS		5.5
Varity_R		0.58
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs564856686; hg19: chr5-81354327; COSMIC: COSV105167073;