Variant 11-128936579-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022112.3(TP53AIP1):c.212C>T(p.Ser71Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000246 in 1,586,704 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

TP53AIP1
NM_022112.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.163

Variant links:

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]

TP53AIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08205363).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP53AIP1	NM_022112.3 link	c.212C>T	p.Ser71Leu	missense_variant	3/4	ENST00000531399.6	NP_071395.2	Q9HCN2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP53AIP1	ENST00000531399.6 link	c.212C>T	p.Ser71Leu	missense_variant	3/4	1	NM_022112.3	ENSP00000432743.1		Q9HCN2-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000375

AC:

AN:

213276

Hom.:

AF XY:

0.0000342

AC XY:

AN XY:

117068

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000612

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000244

AC:

AN:

1434566

Hom.:

Cov.:

AF XY:

0.0000196

AC XY:

AN XY:

712502

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000231

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000235

Gnomad4 OTH exome

AF:

0.0000834

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000349

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2022

The c.212C>T (p.S71L) alteration is located in exon 3 (coding exon 2) of the TP53AIP1 gene. This alteration results from a C to T substitution at nucleotide position 212, causing the serine (S) at amino acid position 71 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.043

.;T;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.60

T;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.082

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-2.7

D;D;D

REVEL

Benign

0.10

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.99

.;D;.

Vest4

0.082

MutPred

0.20

Loss of disorder (P = 0.0072);Loss of disorder (P = 0.0072);Loss of disorder (P = 0.0072);

MVP

0.25

MPC

0.030

ClinPred

0.17

GERP RS

0.70

Varity_R

0.21

gMVP

0.0024

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over