rs9398069

Variant names:

• chr6-106153290-T-C
• rs9398069
• ENST00000636437.1:c.457+48682A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000636437.1(ATG5):​c.457+48682A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 152,032 control chromosomes in the GnomAD database, including 17,181 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (17181 hom., cov: 32)
• Consequence: ATG5 ENST00000636437.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412
• Publications: 10 publications found

Genes affected

ATG5 (HGNC:589): (autophagy related 5) The protein encoded by this gene, in combination with autophagy protein 12, functions as an E1-like activating enzyme in a ubiquitin-like conjugating system. The encoded protein is involved in several cellular processes, including autophagic vesicle formation, mitochondrial quality control after oxidative damage, negative regulation of the innate antiviral immune response, lymphocyte development and proliferation, MHC II antigen presentation, adipocyte differentiation, and apoptosis. Several transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

ATG5 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia, autosomal recessive 25

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG5	ENST00000636437.1	c.457+48682A>G		intron_variant	Intron 6 of 6	5		ENSP00000490376.1
ATG5	ENST00000636335.1	n.457+48682A>G		intron_variant	Intron 6 of 8	5		ENSP00000490221.1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70504 AN: 151914 Hom.: 17131 Cov.: 32

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.441

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.464 AC: 70615 AN: 152032 Hom.: 17181 Cov.: 32 AF XY: 0.466 AC XY: 34661 AN XY: 74338

African (AFR) AF: 0.607 AC: 25166 AN: 41430

American (AMR) AF: 0.422 AC: 6452 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1527 AN: 3470

East Asian (EAS) AF: 0.530 AC: 2743 AN: 5174

South Asian (SAS) AF: 0.513 AC: 2472 AN: 4822

European-Finnish (FIN) AF: 0.392 AC: 4153 AN: 10586

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26677 AN: 67964

Other (OTH) AF: 0.447 AC: 942 AN: 2106

Alfa AF: 0.418 Hom.: 55851

Bravo AF: 0.469

Asia WGS AF: 0.548 AC: 1905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.87
DANN	Benign	0.73
PhyloP100		-0.41

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9398069; hg19: chr6-106601165; COSMIC: COSV60263662;