20-34710077-C-T

Variant names:

• chr20-34710077-C-T
• rs766846796
• NM_021202.3:c.433C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021202.3(TP53INP2):​c.433C>T​(p.Arg145Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000179 in 1,116,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. R145G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: TP53INP2 NM_021202.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.75
• Publications: 0 publications found

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

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=0.3664591).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53INP2	NM_021202.3	MANE Select	c.433C>T	p.Arg145Cys	missense	Exon 5 of 5	NP_067025.1	Q8IXH6
	TP53INP2	NM_001329429.2		c.433C>T	p.Arg145Cys	missense	Exon 5 of 5	NP_001316358.1	Q8IXH6
	TP53INP2	NM_001329430.2		c.433C>T	p.Arg145Cys	missense	Exon 4 of 4	NP_001316359.1	Q8IXH6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53INP2	ENST00000374810.8	TSL:1 MANE Select	c.433C>T	p.Arg145Cys	missense	Exon 5 of 5	ENSP00000363943.3	Q8IXH6
	TP53INP2	ENST00000374809.6	TSL:5	c.433C>T	p.Arg145Cys	missense	Exon 4 of 4	ENSP00000363942.2	Q8IXH6
	TP53INP2	ENST00000894582.1		c.433C>T	p.Arg145Cys	missense	Exon 4 of 4	ENSP00000564641.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000179 AC: 2 AN: 1116204 Hom.: 0 Cov.: 33 AF XY: 0.00000185 AC XY: 1 AN XY: 539182

African (AFR) AF: 0.00 AC: 0 AN: 22782

American (AMR) AF: 0.00 AC: 0 AN: 9234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13806

East Asian (EAS) AF: 0.00 AC: 0 AN: 25324

South Asian (SAS) AF: 0.0000325 AC: 1 AN: 30796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22800

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3014

European-Non Finnish (NFE) AF: 0.00000106 AC: 1 AN: 944450

Other (OTH) AF: 0.00 AC: 0 AN: 43998

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.068	T
Eigen	Benign	0.088
Eigen_PC	Benign	0.0095
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.83	T
M_CAP	Pathogenic	0.40	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.7
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.094
Sift	Benign	0.055	T
Sift4G	Uncertain	0.055	T
Polyphen		1.0	D
Vest4		0.17
MutPred		0.24		Loss of MoRF binding (P = 0.0224)
MVP		0.26
MPC		0.63
ClinPred		0.95	D
GERP RS		3.0
Varity_R		0.12
gMVP		0.19
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs766846796; hg19: chr20-33297881;