1-159063602-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_004833.3(AIM2):c.889A>G(p.Arg297Gly) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AIM2 NM_004833.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.495

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049859613).
• BP6: Variant 1-159063602-T-C is Benign according to our data. Variant chr1-159063602-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2277298.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AIM2	NM_004833.3	c.889A>G	p.Arg297Gly	missense_variant	5/6	ENST00000368130.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AIM2	ENST00000368130.9	c.889A>G	p.Arg297Gly	missense_variant	5/6	1	NM_004833.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 11, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	0.93
Dann	Benign	0.36
DEOGEN2	Benign	0.042	T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00037	N
LIST_S2	Benign	0.40	T;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.050	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-2.6	N;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	6.7	N;N
REVEL	Benign	0.062
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.11
MutPred		0.65		Loss of stability (P = 0.0473);.;
MVP		0.14
MPC		0.26
ClinPred		0.038	T
GERP RS		-2.0
Varity_R		0.21
gMVP		0.085

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr1-159033392;