rs769270327

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7

The NM_000546.6(TP53):c.393C>T(p.Asn131Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TP53
NM_000546.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0280

Publications

56 publications found

Variant links:

COSMIC-nc: COSV52891063

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 Gene-Disease associations (from GenCC):

breast cancer
Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
Li-Fraumeni syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet
Li-Fraumeni syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp
adrenocortical carcinoma, hereditary
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
sarcoma
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
bone marrow failure syndrome 5
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
colorectal cancer
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
choroid plexus carcinoma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TP53 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 17-7675219-G-A is Benign according to our data. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7675219-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 922981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.028 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP53	NM_000546.6 link	c.393C>T	p.Asn131Asn	synonymous_variant	Exon 5 of 11	ENST00000269305.9	NP_000537.3	P04637-1K7PPA8Q53GA5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP53	ENST00000269305.9 link	c.393C>T	p.Asn131Asn	synonymous_variant	Exon 5 of 11	1	NM_000546.6	ENSP00000269305.4		P04637-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461782

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727176

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111940

Other (OTH)

AF:

0.00

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary cancer-predisposing syndrome

Benign:2

Mar 28, 2019

Color Diagnostics, LLC DBA Color Health

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 07, 2019

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Li-Fraumeni syndrome 1

Benign:1

Apr 02, 2025

Myriad Genetics, Inc.

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -

Li-Fraumeni syndrome

Benign:1

May 13, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

9.0

(source)

DANN

Benign

0.67

PhyloP100

0.028

PromoterAI

-0.064

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=97/3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over