rs3734114

Positions:

• chr5-82058570-T-C
• chr5-82058570-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031482.5(ATG10):​c.184T>C​(p.Ser62Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,610,556 control chromosomes in the GnomAD database, including 34,675 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.17 (2506 hom., cov: 31)
  • Exomes 𝑓: 0.20 (32169 hom.)
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0035431683).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG10	NM_031482.5	c.184T>C	p.Ser62Pro	missense_variant	3/8	ENST00000282185.8	NP_113670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG10	ENST00000282185.8	c.184T>C	p.Ser62Pro	missense_variant	3/8	1	NM_031482.5	ENSP00000282185.3

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25325 AN: 151892 Hom.: 2505 Cov.: 31

Gnomad AFR AF: 0.0747

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.168

GnomAD3 exomes AF: 0.206 AC: 51714 AN: 250878 Hom.: 6002 AF XY: 0.219 AC XY: 29744 AN XY: 135588

Gnomad AFR exome AF: 0.0751

Gnomad AMR exome AF: 0.129

Gnomad ASJ exome AF: 0.181

Gnomad EAS exome AF: 0.213

Gnomad SAS exome AF: 0.368

Gnomad FIN exome AF: 0.240

Gnomad NFE exome AF: 0.200

Gnomad OTH exome AF: 0.196

GnomAD4 exome AF: 0.202 AC: 295163 AN: 1458546 Hom.: 32169 Cov.: 31 AF XY: 0.209 AC XY: 151689 AN XY: 725650

Gnomad4 AFR exome AF: 0.0747

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.187

Gnomad4 EAS exome AF: 0.164

Gnomad4 SAS exome AF: 0.367

Gnomad4 FIN exome AF: 0.237

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.197

GnomAD4 genome AF: 0.167 AC: 25326 AN: 152010 Hom.: 2506 Cov.: 31 AF XY: 0.173 AC XY: 12869 AN XY: 74290

Gnomad4 AFR AF: 0.0748

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.165

Alfa AF: 0.195 Hom.: 7472

Bravo AF: 0.151

TwinsUK AF: 0.202 AC: 750

ALSPAC AF: 0.210 AC: 811

ESP6500AA AF: 0.0817 AC: 360

ESP6500EA AF: 0.202 AC: 1736

ExAC AF: 0.209 AC: 25394

Asia WGS AF: 0.262 AC: 910 AN: 3476

EpiCase AF: 0.200

EpiControl AF: 0.200

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.3
DANN	Benign	0.95
DEOGEN2	Benign	0.031	.;T;T;.;T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.51	.;.;T;T;T
MetaRNN	Benign	0.0035	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L;L;L;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.55	N;N;N;N;N
REVEL	Benign	0.028
Sift	Benign	0.29	T;T;T;T;T
Sift4G	Benign	0.16	T;T;T;T;T
Polyphen		0.089	B;B;B;B;.
Vest4		0.17
MPC		0.14
ClinPred		0.0013	T
GERP RS		0.71
Varity_R		0.15
gMVP		0.24

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; COSMIC: COSV56430188;