11-128937692-G-A

Variant names:

• chr11-128937692-G-A
• NM_022112.3:c.127C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022112.3(TP53AIP1):​c.127C>T​(p.His43Tyr) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TP53AIP1 NM_022112.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.365
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10140318).

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.127C>T	p.His43Tyr	missense	Exon 2 of 4	NP_071395.2	Q9HCN2-1
	TP53AIP1	NM_001195194.1		c.127C>T	p.His43Tyr	missense	Exon 1 of 3	NP_001182123.1	Q9HCN2-4
	TP53AIP1	NM_001251964.2		c.127C>T	p.His43Tyr	missense	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.127C>T	p.His43Tyr	missense	Exon 2 of 4	ENSP00000432743.1	Q9HCN2-1
	TP53AIP1	ENST00000530777.5	TSL:1	c.127C>T	p.His43Tyr	missense	Exon 1 of 3	ENSP00000432908.1	Q9HCN2-4
	TP53AIP1	ENST00000602346.5	TSL:1	c.127C>T	p.His43Tyr	missense	Exon 2 of 2	ENSP00000473353.1	Q9HCN2-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.4
DANN	Benign	0.47
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.0031	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.36
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.060
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.96	D
Vest4		0.24
MutPred		0.26		Gain of sheet (P = 0.0344)
MVP		0.061
MPC		0.019
ClinPred		0.30	T
GERP RS		-0.48
PromoterAI		-0.010	Neutral
Varity_R		0.31
gMVP		0.010
Mutation Taster		=100/0	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

hg19: chr11-128807587;