chr5-82058570-T-G

Variant names:

• chr5-82058570-T-G
• rs3734114
• NM_031482.5:c.184T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031482.5(ATG10):​c.184T>G​(p.Ser62Ala) 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. 14/21 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. S62P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ATG10 NM_031482.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.770

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08486557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG10	NM_031482.5	c.184T>G	p.Ser62Ala	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.184T>G	p.Ser62Ala	missense_variant	Exon 3 of 8	1	NM_031482.5	ENSP00000282185.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.9
DANN	Benign	0.92
DEOGEN2	Benign	0.028	.;T;T;.;T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.47	.;.;T;T;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.085	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M;M;M;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.47	N;N;N;N;N
REVEL	Benign	0.029
Sift	Benign	0.54	T;T;T;T;T
Sift4G	Benign	0.19	T;T;T;T;T
Polyphen		0.11	B;B;B;B;.
Vest4		0.15
MutPred		0.28		Loss of disorder (P = 0.0529);Loss of disorder (P = 0.0529);Loss of disorder (P = 0.0529);Loss of disorder (P = 0.0529);Loss of disorder (P = 0.0529);
MVP		0.22
MPC		0.092
ClinPred		0.090	T
GERP RS		0.71
Varity_R		0.049
gMVP		0.16

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: rs3734114; hg19: chr5-81354389;