20-34710162-A-G

Position:

• chr20-34710162-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.52

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4182875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP53INP2	NM_021202.3	c.518A>G	p.Gln173Arg	missense_variant	5/5	ENST00000374810.8	NP_067025.1
TP53INP2	NM_001329429.2	c.518A>G	p.Gln173Arg	missense_variant	5/5		NP_001316358.1
TP53INP2	NM_001329430.2	c.518A>G	p.Gln173Arg	missense_variant	4/4		NP_001316359.1
TP53INP2	NM_001329431.2	c.518A>G	p.Gln173Arg	missense_variant	5/5		NP_001316360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP53INP2	ENST00000374810.8	c.518A>G	p.Gln173Arg	missense_variant	5/5	1	NM_021202.3	ENSP00000363943	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1142036 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 550350

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2023

The c.518A>G (p.Q173R) alteration is located in exon 5 (coding exon 3) of the TP53INP2 gene. This alteration results from a A to G substitution at nucleotide position 518, causing the glutamine (Q) at amino acid position 173 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.70	.;T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.42	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.9	M;M
MutationTaster	Benign	0.99	D;D
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.15
Sift	Benign	0.030	D;D
Sift4G	Uncertain	0.025	D;D
Polyphen		1.0	D;D
Vest4		0.28
MutPred		0.37		Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);
MVP		0.29
MPC		1.7
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.61
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-33297966;