Genetic Variant NM_021202.3:c.518A>G (chr20-34710162-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_021202.3(TP53INP2):c.518A>G(p.Gln173Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TP53INP2
NM_021202.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.52

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4182875).

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.518A>G	p.Gln173Arg	missense	Exon 5 of 5	NP_067025.1	Q8IXH6
TP53INP2	NM_001329429.2		c.518A>G	p.Gln173Arg	missense	Exon 5 of 5	NP_001316358.1	Q8IXH6
TP53INP2	NM_001329430.2		c.518A>G	p.Gln173Arg	missense	Exon 4 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.518A>G	p.Gln173Arg	missense	Exon 5 of 5	ENSP00000363943.3	Q8IXH6
TP53INP2	ENST00000374809.6	TSL:5	c.518A>G	p.Gln173Arg	missense	Exon 4 of 4	ENSP00000363942.2	Q8IXH6
TP53INP2	ENST00000894582.1		c.518A>G	p.Gln173Arg	missense	Exon 4 of 4	ENSP00000564641.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1142036

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

550350

African (AFR)

AF:

0.00

AC:

AN:

23896

American (AMR)

AF:

0.00

AC:

AN:

11816

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16152

East Asian (EAS)

AF:

0.00

AC:

AN:

26888

South Asian (SAS)

AF:

0.00

AC:

AN:

36086

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28306

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4686

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

948436

Other (OTH)

AF:

0.00

AC:

AN:

45770

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.70

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.42

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.9

PhyloP100

5.5

PrimateAI

Pathogenic

0.92

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.15

Sift

Benign

0.030

Sift4G

Uncertain

0.025

Polyphen

1.0

Vest4

0.28

MutPred

0.37

Gain of solvent accessibility (P = 0.0411)

MVP

0.29

MPC

1.7

ClinPred

0.99

GERP RS

4.5

Varity_R

0.61

gMVP

0.62

Mutation Taster

=50/50

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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