rs35619591

Variant names:

• chr11-46668863-G-A
• rs35619591
• NM_001346311.2:c.1399G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-46668863-G-A
• chr11-46668863-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001346311.2(ATG13):​c.1399G>A​(p.Gly467Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00884 in 1,613,856 control chromosomes in the GnomAD database, including 137 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0074 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0090 (126 hom.)
• Consequence: ATG13 NM_001346311.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.33
• Publications: 17 publications found

Genes affected

ATG13 (HGNC:29091): (autophagy related 13) The protein encoded by this gene is an autophagy factor and a target of the TOR kinase signaling pathway. The encoded protein is essential for autophagosome formation and mitophagy. [provided by RefSeq, Oct 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004194081).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00736 (1120/152226) while in subpopulation SAS AF = 0.0228 (110/4816). AF 95% confidence interval is 0.0194. There are 11 homozygotes in GnomAd4. There are 653 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG13	NM_001346311.2	c.1399G>A	p.Gly467Arg	missense_variant	Exon 17 of 19	ENST00000683050.1	NP_001333240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG13	ENST00000683050.1	c.1399G>A	p.Gly467Arg	missense_variant	Exon 17 of 19		NM_001346311.2	ENSP00000507809.1

Frequencies

GnomAD3 genomes AF: 0.00738 AC: 1122 AN: 152108 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0232

Gnomad FIN AF: 0.0295

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00823

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.0106 AC: 2655 AN: 250934 AF XY: 0.0114

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00185

Gnomad ASJ exome AF: 0.00189

Gnomad EAS exome AF: 0.000326

Gnomad FIN exome AF: 0.0291

Gnomad NFE exome AF: 0.0103

Gnomad OTH exome AF: 0.00832

GnomAD4 exome AF: 0.00900 AC: 13151 AN: 1461630 Hom.: 126 Cov.: 31 AF XY: 0.00946 AC XY: 6881 AN XY: 727134

African (AFR) AF: 0.00131 AC: 44 AN: 33480

American (AMR) AF: 0.00174 AC: 78 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00142 AC: 37 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.0214 AC: 1848 AN: 86258

European-Finnish (FIN) AF: 0.0278 AC: 1480 AN: 53208

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5768

European-Non Finnish (NFE) AF: 0.00831 AC: 9235 AN: 1111968

Other (OTH) AF: 0.00682 AC: 412 AN: 60394

GnomAD4 genome AF: 0.00736 AC: 1120 AN: 152226 Hom.: 11 Cov.: 32 AF XY: 0.00878 AC XY: 653 AN XY: 74408

African (AFR) AF: 0.00130 AC: 54 AN: 41530

American (AMR) AF: 0.00477 AC: 73 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3466

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0228 AC: 110 AN: 4816

European-Finnish (FIN) AF: 0.0295 AC: 313 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00823 AC: 560 AN: 68018

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00766 Hom.: 21

Bravo AF: 0.00468

TwinsUK AF: 0.0116 AC: 43

ALSPAC AF: 0.00830 AC: 32

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00779 AC: 67

ExAC AF: 0.0109 AC: 1320

Asia WGS AF: 0.00895 AC: 31 AN: 3478

EpiCase AF: 0.00742

EpiControl AF: 0.00711

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	.;.;T;.;T;.;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.019
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.74	.;T;.;T;T;T;T
MetaRNN	Benign	0.0042	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	.;.;N;.;N;.;.
PhyloP100		4.3
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.060	N;N;N;N;N;N;D
REVEL	Benign	0.026
Sift	Benign	0.71	T;T;T;T;T;T;T
Sift4G	Benign	0.91	T;T;T;T;T;T;D
Polyphen		0.13	B;.;B;B;B;.;.
Vest4		0.23
MutPred		0.40		.;.;Loss of glycosylation at S433 (P = 0.0733);.;Loss of glycosylation at S433 (P = 0.0733);.;.;
MPC		0.47
ClinPred		0.048	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.033
gMVP		0.33
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs35619591; hg19: chr11-46690413; COSMIC: COSV56321993; COSMIC: COSV56321993;