rs1042522

chr17-7676154-G-Achr17-7676154-G-Cchr17-7676154-G-T

• Frequency: Genomes: not found (cov: 31)
• Consequence: TP53 NM_000546.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.44

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant; Number of alleles below threshold, Median coverage is 31.
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr17-7676154-G-C is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.16614896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TP53	NM_000546.6	c.215C>T	p.Pro72Leu	missense_variant	4/11	ENST00000269305.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TP53	ENST00000269305.9	c.215C>T	p.Pro72Leu	missense_variant	4/11	1	NM_000546.6	P1

Frequencies

GnomAD3 genomes Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK:

Submissions by phenotype

Li-Fraumeni syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Sep 01, 2022

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 72 of the TP53 protein (p.Pro72Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 864652). Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is not expected to disrupt TP53 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Uncertain

0.087

D

BayesDel_noAF

Benign

-0.11

Cadd

Benign

6.1

Dann

Benign

0.55

DEOGEN2

Benign

0.018

T;T;.;T;.;.;.;.;.;.;T;.;.;T;T;.

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.33

N

LIST_S2

Uncertain

0.87

D;D;.;.;.;D;D;.;D;D;D;D;D;D;D;D

M_CAP

Uncertain

0.18

D

MetaRNN

Benign

0.17

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Pathogenic

0.86

D

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.40

T

PROVEAN

Benign

-0.66

N;N;.;N;.;.;N;N;.;.;N;.;.;N;.;N

REVEL

Uncertain

0.34

Sift

Benign

0.087

T;T;.;T;.;.;T;D;.;.;T;.;.;T;.;T

Sift4G

Benign

0.48

T;T;T;T;T;T;T;T;T;T;T;T;T;.;T;.

Polyphen

0.29

B;.;.;B;.;B;B;B;.;.;B;.;.;B;.;.

Vest4

0.25

MutPred

0.26

Gain of stability (P = 0.0106);Gain of stability (P = 0.0106);.;Gain of stability (P = 0.0106);.;Gain of stability (P = 0.0106);Gain of stability (P = 0.0106);Gain of stability (P = 0.0106);.;.;Gain of stability (P = 0.0106);.;Gain of stability (P = 0.0106);Gain of stability (P = 0.0106);Gain of stability (P = 0.0106);Gain of stability (P = 0.0106);

MVP

0.89

MPC

0.69

ClinPred

0.045

T

GERP RS

1.9

Varity_R

0.073

gMVP

0.23

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

LitVar

Other links and lift over

dbSNP: rs1042522; hg19: chr17-7579472;