rs6568431

Variant names:

• chr6-106140931-A-C
• rs6568431
• ENST00000636437.1:c.457+61041T>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+61041T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,130 control chromosomes in the GnomAD database, including 28,291 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 0.61 (28291 hom., cov: 33)
• Consequence: ATG5 ENST00000636437.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.759
• Publications: 57 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.642 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+61041T>G		intron_variant	Intron 6 of 6	5		ENSP00000490376.1
ATG5	ENST00000636335.1	n.457+61041T>G		intron_variant	Intron 6 of 8	5		ENSP00000490221.1

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92415 AN: 152012 Hom.: 28261 Cov.: 33

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.644

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.618

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

GnomAD4 genome AF: 0.608 AC: 92509 AN: 152130 Hom.: 28291 Cov.: 33 AF XY: 0.606 AC XY: 45039 AN XY: 74382

African (AFR) AF: 0.591 AC: 24494 AN: 41478

American (AMR) AF: 0.653 AC: 9986 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2055 AN: 3470

East Asian (EAS) AF: 0.646 AC: 3342 AN: 5176

South Asian (SAS) AF: 0.627 AC: 3026 AN: 4824

European-Finnish (FIN) AF: 0.538 AC: 5699 AN: 10586

Middle Eastern (MID) AF: 0.648 AC: 188 AN: 290

European-Non Finnish (NFE) AF: 0.616 AC: 41852 AN: 67982

Other (OTH) AF: 0.618 AC: 1308 AN: 2116

Alfa AF: 0.618 Hom.: 53111

Bravo AF: 0.619

Asia WGS AF: 0.637 AC: 2218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.5
DANN	Benign	0.68
PhyloP100		-0.76

Splicing

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

Other links and lift over

dbSNP: rs6568431; hg19: chr6-106588806; COSMIC: COSV55571756;