dbSNP rs199743434: TP53INP2:p.Glu69Lys (chr20-34709316-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021202.3(TP53INP2):c.205G>A(p.Glu69Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,888 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. E69Q) 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: 9.85

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP53INP2	NM_021202.3 link	c.205G>A	p.Glu69Lys	missense_variant	Exon 4 of 5	ENST00000374810.8	NP_067025.1	Q8IXH6
TP53INP2	NM_001329429.2 link	c.205G>A	p.Glu69Lys	missense_variant	Exon 4 of 5		NP_001316358.1	Q8IXH6
TP53INP2	NM_001329430.2 link	c.205G>A	p.Glu69Lys	missense_variant	Exon 3 of 4		NP_001316359.1	Q8IXH6
TP53INP2	NM_001329431.2 link	c.205G>A	p.Glu69Lys	missense_variant	Exon 4 of 5		NP_001316360.1	Q8IXH6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP53INP2	ENST00000374810.8 link	c.205G>A	p.Glu69Lys	missense_variant	Exon 4 of 5	1	NM_021202.3	ENSP00000363943.3		Q8IXH6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460888

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726778

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.33

T;T;T

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.90

.;D;D

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.64

D;D;D

MetaSVM

Uncertain

0.13

MutationAssessor

Pathogenic

3.0

M;M;.

PrimateAI

Pathogenic

0.96

PROVEAN

Uncertain

-3.5

D;D;D

REVEL

Uncertain

0.55

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.86

MutPred

0.35

Gain of methylation at E69 (P = 0.0079);Gain of methylation at E69 (P = 0.0079);Gain of methylation at E69 (P = 0.0079);

MVP

0.60

MPC

0.92

ClinPred

0.99

GERP RS

4.6

Varity_R

0.90

gMVP

0.67

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over