chr6-106255743-T-C

Variant names:

• chr6-106255743-T-C
• rs3804332
• NM_004849.4:c.479-7499A>G

Variant summary

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

The NM_004849.4(ATG5):​c.479-7499A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0755 in 152,272 control chromosomes in the GnomAD database, including 735 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 0.075 (735 hom., cov: 32)
• Consequence: ATG5 NM_004849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.975
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG5	NM_004849.4	c.479-7499A>G		intron_variant	Intron 5 of 7	ENST00000369076.8	NP_004840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG5	ENST00000369076.8	c.479-7499A>G		intron_variant	Intron 5 of 7	1	NM_004849.4	ENSP00000358072.3

Frequencies

GnomAD3 genomes AF: 0.0755 AC: 11482 AN: 152154 Hom.: 728 Cov.: 32

Gnomad AFR AF: 0.0211

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.0415

Gnomad FIN AF: 0.0503

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.0742

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0755 AC: 11496 AN: 152272 Hom.: 735 Cov.: 32 AF XY: 0.0774 AC XY: 5766 AN XY: 74458

African (AFR) AF: 0.0211 AC: 877 AN: 41552

American (AMR) AF: 0.222 AC: 3386 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 426 AN: 3472

East Asian (EAS) AF: 0.142 AC: 736 AN: 5182

South Asian (SAS) AF: 0.0412 AC: 199 AN: 4834

European-Finnish (FIN) AF: 0.0503 AC: 534 AN: 10616

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 292

European-Non Finnish (NFE) AF: 0.0742 AC: 5047 AN: 68018

Other (OTH) AF: 0.103 AC: 217 AN: 2108

Alfa AF: 0.0756 Hom.: 290

Bravo AF: 0.0925

Asia WGS AF: 0.0790 AC: 276 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.093
DANN	Benign	0.77
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs3804332; hg19: chr6-106703618;