6-106279340-C-T

Variant names:

• chr6-106279340-C-T
• rs3804333
• NM_004849.4:c.478+321G>A

Variant summary

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

The NM_004849.4(ATG5):​c.478+321G>A 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 152,174 control chromosomes in the GnomAD database, including 2,134 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 (2134 hom., cov: 32)
• Consequence: ATG5 NM_004849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190
• Publications: 11 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.196 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.478+321G>A		intron	N/A	NP_004840.1	A9UGY9
	ATG5	NM_001286106.2		c.478+321G>A		intron	N/A	NP_001273035.1	Q9H1Y0-1
	ATG5	NM_001286108.2		c.478+321G>A		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.478+321G>A		intron	N/A	ENSP00000358072.3	Q9H1Y0-1
	ATG5	ENST00000343245.7	TSL:1	c.478+321G>A		intron	N/A	ENSP00000343313.3	Q9H1Y0-1
	ATG5	ENST00000635758.2	TSL:1	c.244+321G>A		intron	N/A	ENSP00000490493.1	Q9H1Y0-2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23398 AN: 152056 Hom.: 2136 Cov.: 32

Gnomad AFR AF: 0.0759

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0473

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.154 AC: 23393 AN: 152174 Hom.: 2134 Cov.: 32 AF XY: 0.154 AC XY: 11456 AN XY: 74398

African (AFR) AF: 0.0757 AC: 3143 AN: 41546

American (AMR) AF: 0.150 AC: 2290 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 557 AN: 3466

East Asian (EAS) AF: 0.0474 AC: 246 AN: 5186

South Asian (SAS) AF: 0.161 AC: 777 AN: 4824

European-Finnish (FIN) AF: 0.220 AC: 2328 AN: 10578

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

European-Non Finnish (NFE) AF: 0.198 AC: 13488 AN: 67980

Other (OTH) AF: 0.144 AC: 303 AN: 2108

Alfa AF: 0.165 Hom.: 1221

Bravo AF: 0.142

Asia WGS AF: 0.0900 AC: 313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.65
PhyloP100		-0.19
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: rs3804333; hg19: chr6-106727215;