NM_004833.3:c.676C>G

Variant names:

• chr1-159066050-G-C
• rs748193319
• NM_004833.3:c.676C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004833.3(AIM2):​c.676C>G​(p.Arg226Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. R226H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: AIM2 NM_004833.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.16
• Publications: 0 publications found

Genes affected

AIM2 (HGNC:357): (absent in melanoma 2) AIM2 is a member of the IFI20X /IFI16 family. It plays a putative role in tumorigenic reversion and may control cell proliferation. Interferon-gamma induces expression of AIM2. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07368013).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004833.3. 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
	AIM2	NM_004833.3	MANE Select	c.676C>G	p.Arg226Gly	missense	Exon 4 of 6	NP_004824.1	O14862
	AIM2	NM_001348247.2		c.361C>G	p.Arg121Gly	missense	Exon 3 of 5	NP_001335176.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIM2	ENST00000368130.9	TSL:1 MANE Select	c.676C>G	p.Arg226Gly	missense	Exon 4 of 6	ENSP00000357112.4	O14862
	AIM2	ENST00000411768.2	TSL:5	c.676C>G	p.Arg226Gly	missense	Exon 7 of 9	ENSP00000512039.1	O14862
	AIM2	ENST00000695580.1		c.676C>G	p.Arg226Gly	missense	Exon 5 of 7	ENSP00000512040.1	O14862

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461840 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.041
DANN	Benign	0.32
DEOGEN2	Benign	0.049	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		-3.2
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.012
Sift	Benign	0.21	T
Sift4G	Benign	0.36	T
Polyphen		0.023	B
Vest4		0.15
MutPred		0.56		Gain of catalytic residue at V227 (P = 0.0319)
MVP		0.12
MPC		0.32
ClinPred		0.077	T
GERP RS		-6.7
Varity_R		0.20
gMVP		0.068
Mutation Taster		=93/7	polymorphism

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: rs748193319; hg19: chr1-159035840;