chr20-34710077-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_021202.3(TP53INP2):​c.433C>G​(p.Arg145Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000254 in 1,267,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: TP53INP2 NM_021202.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.75
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05847439).
• BS2: High AC in GnomAd4 at 40 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.433C>G	p.Arg145Gly	missense	Exon 5 of 5	NP_067025.1	Q8IXH6
	TP53INP2	NM_001329429.2		c.433C>G	p.Arg145Gly	missense	Exon 5 of 5	NP_001316358.1	Q8IXH6
	TP53INP2	NM_001329430.2		c.433C>G	p.Arg145Gly	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>G	p.Arg145Gly	missense	Exon 5 of 5	ENSP00000363943.3	Q8IXH6
	TP53INP2	ENST00000374809.6	TSL:5	c.433C>G	p.Arg145Gly	missense	Exon 4 of 4	ENSP00000363942.2	Q8IXH6
	TP53INP2	ENST00000894582.1		c.433C>G	p.Arg145Gly	missense	Exon 4 of 4	ENSP00000564641.1

Frequencies

GnomAD3 genomes AF: 0.000264 AC: 40 AN: 151496 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.000868

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000473

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000441 AC: 14 AN: 31736 AF XY: 0.000575

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00145

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000582

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.000253 AC: 282 AN: 1116200 Hom.: 0 Cov.: 33 AF XY: 0.000280 AC XY: 151 AN XY: 539180

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

American (AMR) AF: 0.000108 AC: 1 AN: 9234

Ashkenazi Jewish (ASJ) AF: 0.000507 AC: 7 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: 0.000280 AC: 264 AN: 944446

Other (OTH) AF: 0.000205 AC: 9 AN: 43998

GnomAD4 genome AF: 0.000264 AC: 40 AN: 151604 Hom.: 0 Cov.: 32 AF XY: 0.000257 AC XY: 19 AN XY: 74056

African (AFR) AF: 0.00 AC: 0 AN: 41490

American (AMR) AF: 0.000328 AC: 5 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.000868 AC: 3 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10454

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

European-Non Finnish (NFE) AF: 0.000473 AC: 32 AN: 67686

Other (OTH) AF: 0.00 AC: 0 AN: 2102

Alfa AF: 0.000245 Hom.: 0

ExAC AF: 0.000258 AC: 25

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	0.068
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.70	T
M_CAP	Pathogenic	0.38	D
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.7
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.081
Sift	Benign	0.38	T
Sift4G	Benign	0.38	T
Polyphen		0.67	P
Vest4		0.13
MVP		0.21
MPC		0.30
ClinPred		0.098	T
GERP RS		3.0
Varity_R		0.13
gMVP		0.21
Mutation Taster		=82/18	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;