rs933629822

Variant names:

• chr20-34709395-C-A
• rs933629822
• NM_021202.3:c.284C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-34709395-C-A
• chr20-34709395-C-G
• chr20-34709395-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_021202.3(TP53INP2):​c.284C>A​(p.Pro95His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. P95R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TP53INP2 NM_021202.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.00

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.828

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP53INP2	NM_021202.3	c.284C>A	p.Pro95His	missense_variant	Exon 4 of 5	ENST00000374810.8	NP_067025.1
TP53INP2	NM_001329429.2	c.284C>A	p.Pro95His	missense_variant	Exon 4 of 5		NP_001316358.1
TP53INP2	NM_001329430.2	c.284C>A	p.Pro95His	missense_variant	Exon 3 of 4		NP_001316359.1
TP53INP2	NM_001329431.2	c.284C>A	p.Pro95His	missense_variant	Exon 4 of 5		NP_001316360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP53INP2	ENST00000374810.8	c.284C>A	p.Pro95His	missense_variant	Exon 4 of 5	1	NM_021202.3	ENSP00000363943.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T;T;T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	.;D;T
M_CAP	Pathogenic	0.31	D
MetaRNN	Pathogenic	0.83	D;D;D
MetaSVM	Uncertain	0.47	D
MutationAssessor	Pathogenic	3.1	M;M;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-8.4	D;D;D
REVEL	Pathogenic	0.78
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.92
MutPred		0.55		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);.;
MVP		0.73
MPC		0.93
ClinPred		1.0	D
GERP RS		4.6
Varity_R		0.91
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs933629822; hg19: chr20-33297199;