3-112550440-A-G

Variant names:

• chr3-112550440-A-G
• rs2705520
• NM_022488.5:c.165-178T>C

Variant summary

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

The NM_022488.5(ATG3):​c.165-178T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.982 in 152,294 control chromosomes in the GnomAD database, including 73,435 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 0.98 (73435 hom., cov: 32)
• Consequence: ATG3 NM_022488.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.495
• Publications: 9 publications found

Genes affected

ATG3 (HGNC:20962): (autophagy related 3) This gene encodes a ubiquitin-like-conjugating enzyme and is a component of ubiquitination-like systems involved in autophagy, the process of degradation, turnover and recycling of cytoplasmic constituents in eukaryotic cells. This protein is known to play a role in regulation of autophagy during cell death. A pseudogene of this gene is located on chromosome 20. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

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 (AMR) allele frequency at 95% confidence interval = 0.984 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022488.5. 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
	ATG3	NM_022488.5	MANE Select	c.165-178T>C		intron	N/A	NP_071933.2
	ATG3	NM_001278712.2		c.165-178T>C		intron	N/A	NP_001265641.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG3	ENST00000283290.10	TSL:1 MANE Select	c.165-178T>C		intron	N/A	ENSP00000283290.5
	ATG3	ENST00000402314.6	TSL:1	c.165-178T>C		intron	N/A	ENSP00000385943.2
	ATG3	ENST00000495756.5	TSL:1	n.561-178T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.982 AC: 149444 AN: 152176 Hom.: 73388 Cov.: 32

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.993

Gnomad ASJ AF: 0.989

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.988

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.990

Gnomad OTH AF: 0.981

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

GnomAD4 genome AF: 0.982 AC: 149550 AN: 152294 Hom.: 73435 Cov.: 32 AF XY: 0.982 AC XY: 73155 AN XY: 74460

African (AFR) AF: 0.963 AC: 40023 AN: 41544

American (AMR) AF: 0.993 AC: 15187 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.989 AC: 3434 AN: 3472

East Asian (EAS) AF: 0.986 AC: 5114 AN: 5188

South Asian (SAS) AF: 0.988 AC: 4760 AN: 4820

European-Finnish (FIN) AF: 0.982 AC: 10428 AN: 10616

Middle Eastern (MID) AF: 0.976 AC: 285 AN: 292

European-Non Finnish (NFE) AF: 0.990 AC: 67342 AN: 68038

Other (OTH) AF: 0.981 AC: 2074 AN: 2114

Alfa AF: 0.988 Hom.: 86170

Bravo AF: 0.982

Asia WGS AF: 0.978 AC: 3401 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.3
DANN	Benign	0.77
PhyloP100		0.49
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: rs2705520; hg19: chr3-112269287;