NM_021202.3:c.466C>G

Variant names:

• chr20-34710110-C-G
• rs1283359396
• NM_021202.3:c.466C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_021202.3(TP53INP2):​c.466C>G​(p.Leu156Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 1,266,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: TP53INP2 NM_021202.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.672
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.083789736).
• BS2: High AC in GnomAdExome4 at 12 AD gene.

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.466C>G	p.Leu156Val	missense	Exon 5 of 5	NP_067025.1	Q8IXH6
	TP53INP2	NM_001329429.2		c.466C>G	p.Leu156Val	missense	Exon 5 of 5	NP_001316358.1	Q8IXH6
	TP53INP2	NM_001329430.2		c.466C>G	p.Leu156Val	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.466C>G	p.Leu156Val	missense	Exon 5 of 5	ENSP00000363943.3	Q8IXH6
	TP53INP2	ENST00000374809.6	TSL:5	c.466C>G	p.Leu156Val	missense	Exon 4 of 4	ENSP00000363942.2	Q8IXH6
	TP53INP2	ENST00000894582.1		c.466C>G	p.Leu156Val	missense	Exon 4 of 4	ENSP00000564641.1

Frequencies

GnomAD3 genomes AF: 0.0000264 AC: 4 AN: 151736 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000442

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 10268 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000108 AC: 12 AN: 1114242 Hom.: 0 Cov.: 33 AF XY: 0.0000112 AC XY: 6 AN XY: 535584

African (AFR) AF: 0.00 AC: 0 AN: 23334

American (AMR) AF: 0.00 AC: 0 AN: 8460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14168

East Asian (EAS) AF: 0.00 AC: 0 AN: 26682

South Asian (SAS) AF: 0.0000703 AC: 2 AN: 28464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23350

Middle Eastern (MID) AF: 0.000546 AC: 2 AN: 3662

European-Non Finnish (NFE) AF: 0.00000743 AC: 7 AN: 941728

Other (OTH) AF: 0.0000225 AC: 1 AN: 44394

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151844 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74210

African (AFR) AF: 0.00 AC: 0 AN: 41504

American (AMR) AF: 0.00 AC: 0 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67932

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.6
DANN	Benign	0.86
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.54	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.67
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.056
Sift	Uncertain	0.016	D
Sift4G	Benign	0.30	T
Polyphen		0.073	B
Vest4		0.081
MutPred		0.17		Gain of methylation at R159 (P = 0.1111)
MVP		0.15
MPC		1.3
ClinPred		0.060	T
GERP RS		1.9
Varity_R		0.068
gMVP		0.30
Mutation Taster		=89/11	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: rs1283359396; hg19: chr20-33297914;