3-112548546-TG-GA

Variant names:

• chr3-112548546-TG-GA
• NM_022488.5:c.329_330delCAinsTC
• ATG3 p.Thr110Ile

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_022488.5(ATG3):​c.329_330delCAinsTC​(p.Thr110Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T110K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATG3 NM_022488.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.56
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG3	NM_022488.5	MANE Select	c.329_330delCAinsTC	p.Thr110Ile	missense	N/A	NP_071933.2
	ATG3	NM_001278712.2		c.329_330delCAinsTC	p.Thr110Ile	missense	N/A	NP_001265641.1	Q9NT62-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG3	ENST00000283290.10	TSL:1 MANE Select	c.329_330delCAinsTC	p.Thr110Ile	missense	N/A	ENSP00000283290.5	Q9NT62-1
	ATG3	ENST00000402314.6	TSL:1	c.329_330delCAinsTC	p.Thr110Ile	missense	N/A	ENSP00000385943.2	Q9NT62-2
	ATG3	ENST00000495756.5	TSL:1	n.725_726delCAinsTC		non_coding_transcript_exon	Exon 5 of 10

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-112267393;