chr11-128935674-C-G

Variant names:

• chr11-128935674-C-G
• rs372730991
• NM_022112.3:c.292G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022112.3(TP53AIP1):​c.292G>C​(p.Ala98Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000441 in 1,586,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: TP53AIP1 NM_022112.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.555
• Publications: 0 publications found

Genes affected

TP53AIP1 (HGNC:29984): (tumor protein p53 regulated apoptosis inducing protein 1) This gene is specifically expressed in the thymus, and encodes a protein that is localized to the mitochondrion. The expression of this gene is inducible by p53, and it is thought to play an important role in mediating p53-dependent apoptosis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051273912).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022112.3. 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
	TP53AIP1	NM_022112.3	MANE Select	c.292G>C	p.Ala98Pro	missense	Exon 4 of 4	NP_071395.2	Q9HCN2-1
	TP53AIP1	NM_001195194.1		c.280G>C	p.Ala94Pro	missense	Exon 3 of 3	NP_001182123.1	Q9HCN2-4
	TP53AIP1	NM_001251964.2		c.*1818G>C		3_prime_UTR	Exon 2 of 2	NP_001238893.1	Q9HCN2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53AIP1	ENST00000531399.6	TSL:1 MANE Select	c.292G>C	p.Ala98Pro	missense	Exon 4 of 4	ENSP00000432743.1	Q9HCN2-1
	TP53AIP1	ENST00000530777.5	TSL:1	c.280G>C	p.Ala94Pro	missense	Exon 3 of 3	ENSP00000432908.1	Q9HCN2-4
	TP53AIP1	ENST00000602346.5	TSL:1	c.*1818G>C		3_prime_UTR	Exon 2 of 2	ENSP00000473353.1	Q9HCN2-3

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152154 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000944 AC: 2 AN: 211928 AF XY: 0.00000858

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000123

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000349 AC: 5 AN: 1434218 Hom.: 0 Cov.: 32 AF XY: 0.00000140 AC XY: 1 AN XY: 712328

African (AFR) AF: 0.00 AC: 0 AN: 33266

American (AMR) AF: 0.00 AC: 0 AN: 43070

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25898

East Asian (EAS) AF: 0.000127 AC: 5 AN: 39372

South Asian (SAS) AF: 0.00 AC: 0 AN: 83530

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106028

Other (OTH) AF: 0.00 AC: 0 AN: 59906

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152272 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74460

African (AFR) AF: 0.00 AC: 0 AN: 41560

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000175 AC: 2

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.18
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.13
DANN	Benign	0.31
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.56
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.039
Sift	Benign	0.055	T
Sift4G	Benign	0.15	T
Polyphen		0.55	P
Vest4		0.29
MutPred		0.32		Loss of sheet (P = 0.0357)
MVP		0.061
MPC		0.011
ClinPred		0.096	T
GERP RS		-1.8
Varity_R		0.096
gMVP		0.0084
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs372730991; hg19: chr11-128805569;