rs10485352

Variant names:

• chr6-106300336-A-G
• rs10485352
• NM_004849.4:c.237-7230T>C

Variant summary

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

The NM_004849.4(ATG5):​c.237-7230T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.075 in 152,206 control chromosomes in the GnomAD database, including 734 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 (734 hom., cov: 32)
• Consequence: ATG5 NM_004849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.566
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.215 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG5	NM_004849.4	MANE Select	c.237-7230T>C		intron	N/A	NP_004840.1
	ATG5	NM_001286106.2		c.237-7230T>C		intron	N/A	NP_001273035.1
	ATG5	NM_001286108.2		c.237-7230T>C		intron	N/A	NP_001273037.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG5	ENST00000369076.8	TSL:1 MANE Select	c.237-7230T>C		intron	N/A	ENSP00000358072.3
	ATG5	ENST00000343245.7	TSL:1	c.237-7230T>C		intron	N/A	ENSP00000343313.3
	ATG5	ENST00000635758.2	TSL:1	c.3-7230T>C		intron	N/A	ENSP00000490493.1

Frequencies

GnomAD3 genomes AF: 0.0750 AC: 11409 AN: 152088 Hom.: 727 Cov.: 32

Gnomad AFR AF: 0.0209

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.0379

Gnomad FIN AF: 0.0505

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0737

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0750 AC: 11423 AN: 152206 Hom.: 734 Cov.: 32 AF XY: 0.0768 AC XY: 5714 AN XY: 74420

African (AFR) AF: 0.0209 AC: 869 AN: 41560

American (AMR) AF: 0.221 AC: 3380 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 426 AN: 3468

East Asian (EAS) AF: 0.141 AC: 733 AN: 5182

South Asian (SAS) AF: 0.0375 AC: 181 AN: 4824

European-Finnish (FIN) AF: 0.0505 AC: 536 AN: 10604

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0737 AC: 5007 AN: 67960

Other (OTH) AF: 0.103 AC: 218 AN: 2112

Alfa AF: 0.0750 Hom.: 281

Bravo AF: 0.0921

Asia WGS AF: 0.0760 AC: 264 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	6.9
DANN	Benign	0.80
PhyloP100		0.57
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: rs10485352; hg19: chr6-106748211;