chr3-112532743-T-C

Variant names:

• chr3-112532743-T-C
• NM_022488.5:c.901A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022488.5(ATG3):​c.901A>G​(p.Ile301Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,448,136 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ATG3 NM_022488.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.45

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG3	NM_022488.5	c.901A>G	p.Ile301Val	missense_variant	Exon 12 of 12	ENST00000283290.10	NP_071933.2
ATG3	XM_011513074.1	c.640A>G	p.Ile214Val	missense_variant	Exon 12 of 12		XP_011511376.1
ATG3	NM_001278712.2	c.*1453A>G		3_prime_UTR_variant	Exon 11 of 11		NP_001265641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG3	ENST00000283290.10	c.901A>G	p.Ile301Val	missense_variant	Exon 12 of 12	1	NM_022488.5	ENSP00000283290.5
ATG3	ENST00000402314	c.*1453A>G		3_prime_UTR_variant	Exon 11 of 11	1		ENSP00000385943.2
ATG3	ENST00000494571.1	n.2537A>G		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1448136 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 720498

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.901A>G (p.I301V) alteration is located in exon 12 (coding exon 12) of the ATG3 gene. This alteration results from a A to G substitution at nucleotide position 901, causing the isoleucine (I) at amino acid position 301 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.064	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0062	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.94	N
REVEL	Uncertain	0.31
Sift	Benign	0.073	T
Sift4G	Benign	0.22	T
Polyphen		1.0	D
Vest4		0.41
MutPred		0.60		Loss of catalytic residue at I301 (P = 0.1087);
MVP		0.52
MPC		1.4
ClinPred		0.93	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.47

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-112251590;