Genetic Variant TP53AIP1:c.-77+118A>G (chr11-128942676-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022112.3(TP53AIP1):c.-77+118A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 151,998 control chromosomes in the GnomAD database, including 31,848 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.64 ( 31848 hom., cov: 33)

Exomes 𝑓: 0.57 ( 30 hom. )

Failed GnomAD Quality Control

Consequence

TP53AIP1
NM_022112.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0400

Publications

4 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TP53AIP1	NM_022112.3	MANE Select	c.-77+118A>G	intron	N/A	NP_071395.2
TP53AIP1	NM_001251964.2		c.-77+118A>G	intron	N/A	NP_001238893.1
TP53AIP1	NM_001195195.2		c.-77+118A>G	intron	N/A	NP_001182124.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TP53AIP1	ENST00000531399.6	TSL:1 MANE Select	c.-77+118A>G	intron	N/A	ENSP00000432743.1
TP53AIP1	ENST00000602346.5	TSL:1	c.-77+118A>G	intron	N/A	ENSP00000473353.1
TP53AIP1	ENST00000458238.6	TSL:1	c.-77+118A>G	intron	N/A	ENSP00000390694.2

Frequencies

GnomAD3 genomes

AF:

0.639

AC:

97125

AN:

151880

Hom.:

31793

Cov.:

show subpopulations

Gnomad AFR

AF:

0.746

Gnomad AMI

AF:

0.467

Gnomad AMR

AF:

0.730

Gnomad ASJ

AF:

0.707

Gnomad EAS

AF:

0.727

Gnomad SAS

AF:

0.756

Gnomad FIN

AF:

0.459

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.565

Gnomad OTH

AF:

0.684

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.572

AC:

AN:

152

Hom.:

AF XY:

0.609

AC XY:

AN XY:

110

show subpopulations

African (AFR)

AF:

0.833

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.423

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.590

AC:

AN:

100

Other (OTH)

AF:

0.563

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.640

AC:

97237

AN:

151998

Hom.:

31848

Cov.:

AF XY:

0.637

AC XY:

47356

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.746

AC:

30961

AN:

41480

American (AMR)

AF:

0.731

AC:

11162

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.707

AC:

2455

AN:

3470

East Asian (EAS)

AF:

0.726

AC:

3747

AN:

5160

South Asian (SAS)

AF:

0.756

AC:

3647

AN:

4822

European-Finnish (FIN)

AF:

0.459

AC:

4847

AN:

10570

Middle Eastern (MID)

AF:

0.673

AC:

198

AN:

294

European-Non Finnish (NFE)

AF:

0.565

AC:

38343

AN:

67908

Other (OTH)

AF:

0.688

AC:

1451

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1707

3414

5122

6829

8536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

788

1576

2364

3152

3940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.614

Hom.:

38257

Bravo

AF:

0.667

Asia WGS

AF:

0.734

AC:

2549

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

4.5

(source)

DANN

Benign

0.38

PhyloP100

-0.040

PromoterAI

0.045

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over