6-106207742-T-C

Variant names:

• chr6-106207742-T-C
• rs9373839
• NM_004849.4:c.574-5653A>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.574-5653A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 151,948 control chromosomes in the GnomAD database, including 2,132 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 0.15 (2132 hom., cov: 32)
• Consequence: ATG5 NM_004849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70
• Publications: 32 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004849.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG5	NM_004849.4	MANE Select	c.574-5653A>G		intron	N/A	NP_004840.1	A9UGY9
	ATG5	NM_001286106.2		c.574-5653A>G		intron	N/A	NP_001273035.1	Q9H1Y0-1
	ATG5	NM_001286108.2		c.570-5653A>G		intron	N/A	NP_001273037.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG5	ENST00000369076.8	TSL:1 MANE Select	c.574-5653A>G		intron	N/A	ENSP00000358072.3	Q9H1Y0-1
	ATG5	ENST00000343245.7	TSL:1	c.574-5653A>G		intron	N/A	ENSP00000343313.3	Q9H1Y0-1
	ATG5	ENST00000635758.2	TSL:1	c.340-5653A>G		intron	N/A	ENSP00000490493.1	Q9H1Y0-2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23337 AN: 151830 Hom.: 2134 Cov.: 32

Gnomad AFR AF: 0.0725

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.0474

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.154 AC: 23332 AN: 151948 Hom.: 2132 Cov.: 32 AF XY: 0.154 AC XY: 11436 AN XY: 74276

African (AFR) AF: 0.0723 AC: 2998 AN: 41446

American (AMR) AF: 0.150 AC: 2281 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 549 AN: 3470

East Asian (EAS) AF: 0.0475 AC: 245 AN: 5160

South Asian (SAS) AF: 0.162 AC: 778 AN: 4816

European-Finnish (FIN) AF: 0.220 AC: 2319 AN: 10540

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13600 AN: 67948

Other (OTH) AF: 0.143 AC: 302 AN: 2110

Alfa AF: 0.167 Hom.: 991

Bravo AF: 0.142

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	9.5
DANN	Benign	0.44
PhyloP100		1.7
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: rs9373839; hg19: chr6-106655617;