rs34419602

Variant names:

• chr1-159065931-A-C
• rs34419602
• NM_004833.3:c.795T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-159065931-A-C
• chr1-159065931-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004833.3(AIM2):​c.795T>G​(p.Asn265Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N265N) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: AIM2 NM_004833.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3686344).

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.795T>G	p.Asn265Lys	missense	Exon 4 of 6	NP_004824.1	O14862
	AIM2	NM_001348247.2		c.480T>G	p.Asn160Lys	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.795T>G	p.Asn265Lys	missense	Exon 4 of 6	ENSP00000357112.4	O14862
	AIM2	ENST00000411768.2	TSL:5	c.795T>G	p.Asn265Lys	missense	Exon 7 of 9	ENSP00000512039.1	O14862
	AIM2	ENST00000695580.1		c.795T>G	p.Asn265Lys	missense	Exon 5 of 7	ENSP00000512040.1	O14862

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459260 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725698

African (AFR) AF: 0.00 AC: 0 AN: 33326

American (AMR) AF: 0.00 AC: 0 AN: 44408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26018

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 85734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110702

Other (OTH) AF: 0.00 AC: 0 AN: 60294

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.9
DANN	Benign	0.96
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		-0.23
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.057
Sift	Benign	0.25	T
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.49
MutPred		0.73		Gain of methylation at N265 (P = 0.0044)
MVP		0.35
MPC		0.82
ClinPred		0.50	D
GERP RS		-1.9
Varity_R		0.33
gMVP		0.069
Mutation Taster		=73/27	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: rs34419602; hg19: chr1-159035721;