Variant 17-7674957-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_000546.6(TP53):c.574C>G(p.Gln192Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

TP53
NM_000546.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.13

Variant links:

Genes affected

TP53 (HGNC:11998): (tumor protein p53) This gene encodes a tumor suppressor protein containing transcriptional activation, DNA binding, and oligomerization domains. The encoded protein responds to diverse cellular stresses to regulate expression of target genes, thereby inducing cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. Mutations in this gene are associated with a variety of human cancers, including hereditary cancers such as Li-Fraumeni syndrome. Alternative splicing of this gene and the use of alternate promoters result in multiple transcript variants and isoforms. Additional isoforms have also been shown to result from the use of alternate translation initiation codons from identical transcript variants (PMIDs: 12032546, 20937277). [provided by RefSeq, Dec 2016]

TP53 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a region_of_interest Interaction with AXIN1 (size 176) in uniprot entity P53_HUMAN there are 53 pathogenic changes around while only 3 benign (95%) in NM_000546.6

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP53	NM_000546.6 linkuse as main transcript	c.574C>G	p.Gln192Glu	missense_variant	6/11	ENST00000269305.9	NP_000537.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP53	ENST00000269305.9 linkuse as main transcript	c.574C>G	p.Gln192Glu	missense_variant	6/11	1	NM_000546.6	ENSP00000269305	P1	P04637-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Adrenocortical carcinoma, hereditary

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

May 26, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

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

Eigen

Benign

-0.064

Eigen_PC

Benign

-0.049

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.81

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

M_CAP

Pathogenic

0.54

MetaRNN

Uncertain

0.66

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Benign

1.8

.;.;.;.;.;.;.;.;.;L;.;L;L;L;.;.;L;.;.;.;.

MutationTaster

Benign

0.94

D;D;D;D;D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.63

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

REVEL

Uncertain

0.56

Sift

Uncertain

0.010

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

Sift4G

Uncertain

0.053

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

Polyphen

0.96

D;.;.;.;.;.;.;.;.;B;.;B;B;B;.;.;B;.;.;.;P

Vest4

0.51

MutPred

0.51

Gain of disorder (P = 0.0635);Gain of disorder (P = 0.0635);.;.;.;.;.;.;.;Gain of disorder (P = 0.0635);.;Gain of disorder (P = 0.0635);Gain of disorder (P = 0.0635);Gain of disorder (P = 0.0635);.;.;Gain of disorder (P = 0.0635);.;.;.;.;

MVP

0.86

MPC

1.5

ClinPred

0.76

GERP RS

3.4

Varity_R

0.75

gMVP

0.40

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over