NM_004881.5:c.813T>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_004881.5(TP53I3):c.813T>G(p.Asn271Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000186 in 1,613,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N271D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00093 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

TP53I3
NM_004881.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.988

Publications

0 publications found

Variant links:

Genes affected

TP53I3 (HGNC:19373): (tumor protein p53 inducible protein 3) The protein encoded by this gene is similar to oxidoreductases, which are enzymes involved in cellular responses to oxidative stresses and irradiation. This gene is induced by the tumor suppressor p53 and is thought to be involved in p53-mediated cell death. It contains a p53 consensus binding site in its promoter region and a downstream pentanucleotide microsatellite sequence. P53 has been shown to transcriptionally activate this gene by interacting with the downstream pentanucleotide microsatellite sequence. The microsatellite is polymorphic, with a varying number of pentanucleotide repeats directly correlated with the extent of transcriptional activation by p53. It has been suggested that the microsatellite polymorphism may be associated with differential susceptibility to cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

TP53I3 links:

FAM228B (HGNC:24736): (family with sequence similarity 228 member B)

FAM228B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039865375).

BP6

Variant 2-24079447-A-C is Benign according to our data. Variant chr2-24079447-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3039519.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004881.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TP53I3	NM_004881.5	MANE Select	c.813T>G	p.Asn271Lys	missense	Exon 4 of 5	NP_004872.2
TP53I3	NM_147184.4		c.813T>G	p.Asn271Lys	missense	Exon 5 of 6	NP_671713.1	Q53FA7-1
TP53I3	NM_001206802.2		c.619+1372T>G		intron	N/A	NP_001193731.1	Q53FA7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TP53I3	ENST00000238721.9	TSL:1 MANE Select	c.813T>G	p.Asn271Lys	missense	Exon 4 of 5	ENSP00000238721.4	Q53FA7-1
TP53I3	ENST00000335934.8	TSL:1	c.813T>G	p.Asn271Lys	missense	Exon 5 of 6	ENSP00000337834.4	Q53FA7-1
TP53I3	ENST00000407482.5	TSL:1	c.619+1372T>G		intron	N/A	ENSP00000384414.1	Q53FA7-2

Frequencies

GnomAD3 genomes

AF:

0.000927

AC:

141

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00321

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000279

AC:

AN:

251326

AF XY:

0.000214

show subpopulations

Gnomad AFR exome

AF:

0.00388

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000109

AC:

159

AN:

1461672

Hom.:

Cov.:

AF XY:

0.0000908

AC XY:

AN XY:

727150

show subpopulations

African (AFR)

AF:

0.00406

AC:

136

AN:

33462

American (AMR)

AF:

0.000179

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111894

Other (OTH)

AF:

0.000182

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000927

AC:

141

AN:

152150

Hom.:

Cov.:

AF XY:

0.000833

AC XY:

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.00320

AC:

133

AN:

41510

American (AMR)

AF:

0.000393

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67994

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000419

Hom.:

Bravo

AF:

0.00119

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000354

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

TP53I3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.4

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.019

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.54

M_CAP

Benign

0.0062

MetaRNN

Benign

0.0040

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.41

PhyloP100

0.99

PrimateAI

Benign

0.26

PROVEAN

Benign

1.3

REVEL

Benign

0.022

Sift

Benign

0.95

Sift4G

Benign

0.93

Polyphen

0.0

Vest4

0.11

MutPred

0.35

Gain of MoRF binding (P = 0.0319)

MVP

0.14

MPC

0.37

ClinPred

0.011

GERP RS

-1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.093

gMVP

0.37

Mutation Taster

=84/16

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over