Genetic Variant NM_021202.3:c.-166-269T>C (chr20-34705089-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021202.3(TP53INP2):c.-166-269T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 152,050 control chromosomes in the GnomAD database, including 20,194 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.49 ( 20194 hom., cov: 32)

Consequence

TP53INP2
NM_021202.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.169

Publications

9 publications found

Variant links:

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]

TP53INP2 links:

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]

NCOA6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TP53INP2	NM_021202.3 link	c.-166-269T>C	intron_variant	Intron 1 of 4	ENST00000374810.8	NP_067025.1	Q8IXH6
TP53INP2	NM_001329429.2 link	c.-148-269T>C	intron_variant	Intron 1 of 4		NP_001316358.1	Q8IXH6
TP53INP2	NM_001329430.2 link	c.-50+577T>C	intron_variant	Intron 1 of 3		NP_001316359.1	Q8IXH6
TP53INP2	NM_001329431.2 link	c.-166-269T>C	intron_variant	Intron 1 of 4		NP_001316360.1	Q8IXH6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP53INP2	ENST00000374810.8 link	c.-166-269T>C		intron_variant	Intron 1 of 4	1	NM_021202.3	ENSP00000363943.3		Q8IXH6

Frequencies

GnomAD3 genomes

AF:

0.486

AC:

73886

AN:

151932

Hom.:

20153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.745

Gnomad AMI

AF:

0.375

Gnomad AMR

AF:

0.349

Gnomad ASJ

AF:

0.457

Gnomad EAS

AF:

0.241

Gnomad SAS

AF:

0.365

Gnomad FIN

AF:

0.442

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.398

Gnomad OTH

AF:

0.454

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.486

AC:

73972

AN:

152050

Hom.:

20194

Cov.:

AF XY:

0.483

AC XY:

35884

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.745

AC:

30910

AN:

41488

American (AMR)

AF:

0.348

AC:

5323

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.457

AC:

1583

AN:

3464

East Asian (EAS)

AF:

0.240

AC:

1239

AN:

5158

South Asian (SAS)

AF:

0.363

AC:

1753

AN:

4828

European-Finnish (FIN)

AF:

0.442

AC:

4671

AN:

10560

Middle Eastern (MID)

AF:

0.459

AC:

135

AN:

294

European-Non Finnish (NFE)

AF:

0.398

AC:

27056

AN:

67952

Other (OTH)

AF:

0.456

AC:

961

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1767

3534

5302

7069

8836

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.441

Hom.:

3564

Bravo

AF:

0.488

Asia WGS

AF:

0.338

AC:

1178

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

9.0

(source)

DANN

Benign

0.82

PhyloP100

-0.17

PromoterAI

-0.00060

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over