rs1403910089

Variant names:

• chr20-34710075-G-A
• rs1403910089
• NM_021202.3:c.431G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-34710075-G-A
• chr20-34710075-G-T

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.431G>A​(p.Arg144His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000556 in 1,258,560 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 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000054 (0 hom.)
• Consequence: TP53INP2 NM_021202.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.527
• 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=0.10461819).
• BS2: High AC in GnomAdExome4 at 6 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.431G>A	p.Arg144His	missense	Exon 5 of 5	NP_067025.1	Q8IXH6
	TP53INP2	NM_001329429.2		c.431G>A	p.Arg144His	missense	Exon 5 of 5	NP_001316358.1	Q8IXH6
	TP53INP2	NM_001329430.2		c.431G>A	p.Arg144His	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.431G>A	p.Arg144His	missense	Exon 5 of 5	ENSP00000363943.3	Q8IXH6
	TP53INP2	ENST00000374809.6	TSL:5	c.431G>A	p.Arg144His	missense	Exon 4 of 4	ENSP00000363942.2	Q8IXH6
	TP53INP2	ENST00000894582.1		c.431G>A	p.Arg144His	missense	Exon 4 of 4	ENSP00000564641.1

Frequencies

GnomAD3 genomes AF: 0.00000662 AC: 1 AN: 151014 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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000334 AC: 1 AN: 29940 AF XY: 0.0000553

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: 0.00000542 AC: 6 AN: 1107546 Hom.: 0 Cov.: 32 AF XY: 0.00000935 AC XY: 5 AN XY: 534544

African (AFR) AF: 0.00 AC: 0 AN: 22586

American (AMR) AF: 0.00 AC: 0 AN: 8884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13486

East Asian (EAS) AF: 0.00 AC: 0 AN: 24810

South Asian (SAS) AF: 0.00 AC: 0 AN: 30030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2950

European-Non Finnish (NFE) AF: 0.00000639 AC: 6 AN: 939182

Other (OTH) AF: 0.00 AC: 0 AN: 43514

GnomAD4 genome AF: 0.00000662 AC: 1 AN: 151014 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73678

African (AFR) AF: 0.00 AC: 0 AN: 41294

American (AMR) AF: 0.00 AC: 0 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67524

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.0000843 Hom.: 0

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	0.096
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.62	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.53
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.017
Sift	Benign	0.083	T
Sift4G	Benign	0.21	T
Polyphen		0.0010	B
Vest4		0.039
MutPred		0.25		Gain of helix (P = 0.027)
MVP		0.048
MPC		0.29
ClinPred		0.055	T
GERP RS		-0.10
Varity_R		0.027
gMVP		0.17
Mutation Taster		=95/5	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: rs1403910089; hg19: chr20-33297879; COSMIC: COSV62864615; COSMIC: COSV62864615;