Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_000546.5(TP53):c.572C>G (p.Pro191Arg)

CA000272

127816 (ClinVar)

Gene: TP53

Condition: Li-Fraumeni syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: dd649552-60d0-4411-92ac-361dc7acac10

Approved on: 2022-06-21

Published on: 2022-06-27

HGVS expressions

NM_000546.5:c.572C>G

NM_000546.5(TP53):c.572C>G (p.Pro191Arg)

NC_000017.11:g.7674959G>C

CM000679.2:g.7674959G>C

NC_000017.10:g.7578277G>C

CM000679.1:g.7578277G>C

NC_000017.9:g.7519002G>C

NG_017013.2:g.17592C>G

ENST00000269305.9:c.572C>G

ENST00000269305.8:c.572C>G

ENST00000359597.8:n.572C>G

ENST00000413465.6:n.572C>G

ENST00000420246.6:c.572C>G

ENST00000445888.6:c.572C>G

ENST00000455263.6:c.572C>G

ENST00000504290.5:c.176C>G

ENST00000504937.5:c.176C>G

ENST00000505014.5:n.828C>G

ENST00000509690.5:c.176C>G

ENST00000510385.5:c.176C>G

ENST00000514944.5:c.293C>G

ENST00000574684.1:n.67+94C>G

ENST00000610292.4:c.455C>G

ENST00000610538.4:c.455C>G

ENST00000610623.4:c.95C>G

ENST00000615910.4:n.539C>G

ENST00000617185.4:c.572C>G

ENST00000618944.4:c.95C>G

ENST00000619186.4:c.95C>G

ENST00000619485.4:c.455C>G

ENST00000620739.4:c.455C>G

ENST00000622645.4:c.455C>G

ENST00000635293.1:c.455C>G

NM_001126112.2:c.572C>G

NM_001126113.2:c.572C>G

NM_001126114.2:c.572C>G

NM_001126115.1:c.176C>G

NM_001126116.1:c.176C>G

NM_001126117.1:c.176C>G

NM_001126118.1:c.455C>G

NM_001276695.1:c.455C>G

NM_001276696.1:c.455C>G

NM_001276697.1:c.95C>G

NM_001276698.1:c.95C>G

NM_001276699.1:c.95C>G

NM_001276760.1:c.455C>G

NM_001276761.1:c.455C>G

NM_001276695.2:c.455C>G

NM_001276696.2:c.455C>G

NM_001276697.2:c.95C>G

NM_001276698.2:c.95C>G

NM_001276699.2:c.95C>G

NM_001276760.2:c.455C>G

NM_001276761.2:c.455C>G

NM_000546.6:c.572C>G

NM_001126112.3:c.572C>G

NM_001126113.3:c.572C>G

NM_001126114.3:c.572C>G

NM_001126115.2:c.176C>G

NM_001126116.2:c.176C>G

NM_001126117.2:c.176C>G

NM_001126118.2:c.455C>G

NM_001276695.3:c.455C>G

NM_001276696.3:c.455C>G

NM_001276697.3:c.95C>G

NM_001276698.3:c.95C>G

NM_001276699.3:c.95C>G

NM_001276760.3:c.455C>G

NM_001276761.3:c.455C>G

NM_000546.6(TP53):c.572C>G (p.Pro191Arg)

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"

BS3

PS1 PS2 PS4 PS3 BA1 PP3 PP1 PM5 PM1 PM6 PM2 BS4 BS1 BS2 BP7 BP5 BP2 BP4 PVS1

Evidence Links 0

Expert Panel

TP53 VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

TP53 VCEP

Transactivation assays show supertransactivation function according to Kato, et al. and there is no evidence of a dominant negative effect or loss of function according to Giacomelli, et al. (BS3; PMID: 12826609, 30224644). In summary, TP53 c.572C>G (p.Pro191Arg) meets criteria to be classified as likely benign for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: BS3

BS3

Kato supertrans; Kotler retained function; NO DNE + no LOF on Giacomelli. Said et al. paper with 30% reduction in luciferase assay; partially functional.

PS1

none reported

PS2

no reports

PS4

Variant found in a family with angiomatoid fibrous histiocytoma(?) in a 10 year old with the variant, and ependymoma in a 10 yr old sibling who did not have the variant, an unaffected sibling with the variant, and a father with the variant and papillary thyroid cancer at age 38. Case not used as family did not have strong LFS phenotype and unclear segregation in the family (PMID: 27297285). Internal lab had one patient that may meet Chompret (breast cancer at young age) but age could not be confirmed. Not enough to meet.

PS3

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BA1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP3

Bayesdel is 0.0942 and AGVGD is C35 Not met

PP1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM5

no pathogenic entries in ClinVar - other entries mined from Uniprot no AA subs are considered pathogneic - there are two frameshifts

PM1

no entry in cancerhotspots.org; not a designated hotspot

PM6

no reports

PM2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS4

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BP7

predicted possible new donor site by Human Splicing finder

BP5

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BP2

no reported instances

BP4

Bayesdel is 0.0942 and AGVGD is C35

PVS1

missense

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