chr6-106146349-T-C

Variant names:

• chr6-106146349-T-C
• rs742109
• ENST00000636437.1:c.457+55623A>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+55623A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 151,930 control chromosomes in the GnomAD database, including 28,145 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 0.60 (28145 hom., cov: 31)
• Consequence: ATG5 ENST00000636437.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644
• 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=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.814 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+55623A>G		intron_variant	Intron 6 of 6	5		ENSP00000490376.1
ATG5	ENST00000636335.1	n.457+55623A>G		intron_variant	Intron 6 of 8	5		ENSP00000490221.1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91784 AN: 151812 Hom.: 28117 Cov.: 31

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.605 AC: 91849 AN: 151930 Hom.: 28145 Cov.: 31 AF XY: 0.610 AC XY: 45312 AN XY: 74272

African (AFR) AF: 0.539 AC: 22320 AN: 41418

American (AMR) AF: 0.649 AC: 9913 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2071 AN: 3470

East Asian (EAS) AF: 0.756 AC: 3898 AN: 5158

South Asian (SAS) AF: 0.836 AC: 4028 AN: 4818

European-Finnish (FIN) AF: 0.616 AC: 6495 AN: 10544

Middle Eastern (MID) AF: 0.640 AC: 187 AN: 292

European-Non Finnish (NFE) AF: 0.605 AC: 41119 AN: 67944

Other (OTH) AF: 0.602 AC: 1271 AN: 2110

Alfa AF: 0.605 Hom.: 84511

Bravo AF: 0.599

Asia WGS AF: 0.783 AC: 2722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.95
DANN	Benign	0.80
PhyloP100		-0.64

Splicing

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

Other links and lift over

dbSNP: rs742109; hg19: chr6-106594224; COSMIC: COSV60263628;