1-159066178-G-T

Variant names:

• chr1-159066178-G-T
• rs768127211
• NM_004833.3:c.548C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004833.3(AIM2):​c.548C>A​(p.Thr183Lys) 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 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. T183I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AIM2 NM_004833.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.370
• Publications: 1 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.831

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.548C>A	p.Thr183Lys	missense	Exon 4 of 6	NP_004824.1	O14862
	AIM2	NM_001348247.2		c.233C>A	p.Thr78Lys	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.548C>A	p.Thr183Lys	missense	Exon 4 of 6	ENSP00000357112.4	O14862
	AIM2	ENST00000411768.2	TSL:5	c.548C>A	p.Thr183Lys	missense	Exon 7 of 9	ENSP00000512039.1	O14862
	AIM2	ENST00000695580.1		c.548C>A	p.Thr183Lys	missense	Exon 5 of 7	ENSP00000512040.1	O14862

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 251242 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.000264 AC: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Benign	0.93
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0052	T
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		0.37
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.059
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.37
MutPred		0.83		Gain of solvent accessibility (P = 0.012)
MVP		0.53
MPC		0.74
ClinPred		0.82	D
GERP RS		0.20
Varity_R		0.55
gMVP		0.44
Mutation Taster		=96/4	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: rs768127211; hg19: chr1-159035968; COSMIC: COSV63699296; COSMIC: COSV63699296;