chr1-159066287-C-T

Variant names:

• chr1-159066287-C-T
• rs2101967997
• NM_004833.3:c.439G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PM1 PM2 BP4_Strong

The NM_004833.3(AIM2):​c.439G>A​(p.Glu147Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AIM2 NM_004833.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.473
• 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.

• PM1: In a mutagenesis_site Strongly reduced ability to homooligomerize upon double-stranded DNA (dsDNA)-binding. (size 0) in uniprot entity AIM2_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049512982).

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.439G>A	p.Glu147Lys	missense	Exon 4 of 6	NP_004824.1	O14862
	AIM2	NM_001348247.2		c.124G>A	p.Glu42Lys	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.439G>A	p.Glu147Lys	missense	Exon 4 of 6	ENSP00000357112.4	O14862
	AIM2	ENST00000411768.2	TSL:5	c.439G>A	p.Glu147Lys	missense	Exon 7 of 9	ENSP00000512039.1	O14862
	AIM2	ENST00000695580.1		c.439G>A	p.Glu147Lys	missense	Exon 5 of 7	ENSP00000512040.1	O14862

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.7
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.47
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.0090
Sift	Benign	0.62	T
Sift4G	Benign	0.24	T
Polyphen		0.011	B
Vest4		0.11
MutPred		0.32		Gain of MoRF binding (P = 0.003)
MVP		0.28
MPC		0.24
ClinPred		0.088	T
GERP RS		-1.1
Varity_R		0.067
gMVP		0.11
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2101967997; hg19: chr1-159036077;