Genetic Variant NM_021202.3:c.284C>T (chr20-34709395-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_021202.3(TP53INP2):c.284C>T(p.Pro95Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P95R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TP53INP2
NM_021202.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.00

Publications

0 publications found

Variant links:

Genes affected

TP53INP2 (HGNC:16104): (tumor protein p53 inducible nuclear protein 2) The protein encoded by this gene promotes autophagy and is essential for proper autophagosome formation and processing. In addition, the encoded protein can enhance rDNA transcription by helping in the assembly of the POLR1/RNA polymerase I preinitiation complex. Finally, this protein serves as a transcriptional activator for some genes. [provided by RefSeq, Jul 2016]

TP53INP2 links:

NCOA6 (HGNC:15936): (nuclear receptor coactivator 6) The protein encoded by this gene is a transcriptional coactivator that can interact with nuclear hormone receptors to enhance their transcriptional activator functions. This protein has been shown to be involved in the hormone-dependent coactivation of several receptors, including prostanoid, retinoid, vitamin D3, thyroid hormone, and steroid receptors. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jun 2011]

NCOA6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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, 0.832

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021202.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TP53INP2	NM_021202.3	MANE Select	c.284C>T	p.Pro95Leu	missense	Exon 4 of 5	NP_067025.1	Q8IXH6
TP53INP2	NM_001329429.2		c.284C>T	p.Pro95Leu	missense	Exon 4 of 5	NP_001316358.1	Q8IXH6
TP53INP2	NM_001329430.2		c.284C>T	p.Pro95Leu	missense	Exon 3 of 4	NP_001316359.1	Q8IXH6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TP53INP2	ENST00000374810.8	TSL:1 MANE Select	c.284C>T	p.Pro95Leu	missense	Exon 4 of 5	ENSP00000363943.3	Q8IXH6
TP53INP2	ENST00000374809.6	TSL:5	c.284C>T	p.Pro95Leu	missense	Exon 3 of 4	ENSP00000363942.2	Q8IXH6
TP53INP2	ENST00000894582.1		c.284C>T	p.Pro95Leu	missense	Exon 3 of 4	ENSP00000564641.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461626

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727146

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53356

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111868

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Pathogenic

0.38

BayesDel_noAF

Pathogenic

0.31

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.35

MetaRNN

Pathogenic

0.83

MetaSVM

Uncertain

0.47

MutationAssessor

Uncertain

2.8

PhyloP100

6.0

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-9.4

REVEL

Pathogenic

0.77

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.93

MutPred

0.58

Loss of disorder (P = 0.0283)

MVP

0.75

MPC

0.87

ClinPred

1.0

GERP RS

4.6

Varity_R

0.89

gMVP

0.67

Mutation Taster

=39/61

disease causing

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over