rs199743434

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

10
7
2

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]
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]

Genome browser will be placed here

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
TP53INP2NM_021202.3 linkc.205G>A p.Glu69Lys missense_variant Exon 4 of 5 ENST00000374810.8 NP_067025.1 Q8IXH6
TP53INP2NM_001329429.2 linkc.205G>A p.Glu69Lys missense_variant Exon 4 of 5 NP_001316358.1 Q8IXH6
TP53INP2NM_001329430.2 linkc.205G>A p.Glu69Lys missense_variant Exon 3 of 4 NP_001316359.1 Q8IXH6
TP53INP2NM_001329431.2 linkc.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
TP53INP2ENST00000374810.8 linkc.205G>A p.Glu69Lys missense_variant Exon 4 of 5 1 NM_021202.3 ENSP00000363943.3 Q8IXH6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460888
Hom.:
0
Cov.:
36
AF XY:
0.00
AC XY:
0
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.:
32

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
D
BayesDel_noAF
Pathogenic
0.26
CADD
Pathogenic
34
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
D
LIST_S2
Uncertain
0.90
.;D;D
M_CAP
Uncertain
0.13
D
MetaRNN
Uncertain
0.64
D;D;D
MetaSVM
Uncertain
0.13
D
MutationAssessor
Pathogenic
3.0
M;M;.
PrimateAI
Pathogenic
0.96
D
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
D
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.

Other links and lift over

hg19: chr20-33297120; API