rs145779112

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate

The NM_004833.3(AIM2):​c.932G>T​(p.Arg311Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R311G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

AIM2
NM_004833.3 missense

Scores

2
4
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.242
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM1
In a mutagenesis_site Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337. (size 0) in uniprot entity AIM2_HUMAN
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.863

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AIM2NM_004833.3 linkc.932G>T p.Arg311Leu missense_variant Exon 5 of 6 ENST00000368130.9 NP_004824.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AIM2ENST00000368130.9 linkc.932G>T p.Arg311Leu missense_variant Exon 5 of 6 1 NM_004833.3 ENSP00000357112.4 O14862

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152164
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152164
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.060
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.28
T
Eigen
Benign
-0.55
Eigen_PC
Benign
-0.86
FATHMM_MKL
Benign
0.019
N
LIST_S2
Benign
0.53
T
M_CAP
Benign
0.0060
T
MetaRNN
Pathogenic
0.86
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.6
M
PrimateAI
Benign
0.20
T
PROVEAN
Pathogenic
-5.3
D
REVEL
Benign
0.16
Sift
Uncertain
0.0050
D
Sift4G
Uncertain
0.0090
D
Polyphen
1.0
D
Vest4
0.62
MutPred
0.67
Loss of MoRF binding (P = 0.0536);
MVP
0.44
MPC
0.82
ClinPred
0.99
D
GERP RS
-2.9
Varity_R
0.45
gMVP
0.11

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs145779112; hg19: chr1-159033349; API