NM_004881.5:c.539T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004881.5(TP53I3):​c.539T>C​(p.Met180Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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. M180K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

TP53I3
NM_004881.5 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.92
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]
FAM228B (HGNC:24736): (family with sequence similarity 228 member B)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06923187).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TP53I3NM_004881.5 linkc.539T>C p.Met180Thr missense_variant Exon 3 of 5 ENST00000238721.9 NP_004872.2 Q53FA7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TP53I3ENST00000238721.9 linkc.539T>C p.Met180Thr missense_variant Exon 3 of 5 1 NM_004881.5 ENSP00000238721.4 Q53FA7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461894
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
15
DANN
Benign
0.90
DEOGEN2
Benign
0.027
T;T;.;T
Eigen
Benign
-0.67
Eigen_PC
Benign
-0.54
FATHMM_MKL
Benign
0.30
N
LIST_S2
Benign
0.70
.;T;T;T
M_CAP
Benign
0.0041
T
MetaRNN
Benign
0.069
T;T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.26
N;N;N;.
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-0.41
N;N;N;N
REVEL
Benign
0.037
Sift
Benign
0.50
T;T;T;T
Sift4G
Benign
0.42
T;T;T;T
Polyphen
0.0
B;B;B;.
Vest4
0.32
MutPred
0.64
Gain of ubiquitination at K176 (P = 0.0651);Gain of ubiquitination at K176 (P = 0.0651);Gain of ubiquitination at K176 (P = 0.0651);.;
MVP
0.21
MPC
0.37
ClinPred
0.17
T
GERP RS
2.8
Varity_R
0.063
gMVP
0.73

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-24303769; API