Evidence Repository
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
  • See Evidence submitted by expert panel for details.

Variant: NM_000546.5(TP53):c.946C>A (p.Pro316Thr)

CA001212

230382 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: f2e706ef-eea4-48c8-917b-970c7c07543c

HGVS expressions

NM_000546.5:c.946C>A
NM_000546.5(TP53):c.946C>A (p.Pro316Thr)
NC_000017.11:g.7673582G>T
CM000679.2:g.7673582G>T
NC_000017.10:g.7576900G>T
CM000679.1:g.7576900G>T
NC_000017.9:g.7517625G>T
NG_017013.2:g.18969C>A
ENST00000269305.9:c.946C>A
ENST00000269305.8:c.946C>A
ENST00000359597.8:n.946C>A
ENST00000413465.6:n.782+599C>A
ENST00000420246.6:c.946C>A
ENST00000445888.6:c.946C>A
ENST00000455263.6:c.946C>A
ENST00000504290.5:c.550C>A
ENST00000504937.5:c.550C>A
ENST00000509690.5:c.550C>A
ENST00000510385.5:c.550C>A
ENST00000576024.1:n.6C>A
ENST00000610292.4:c.829C>A
ENST00000610538.4:c.829C>A
ENST00000610623.4:c.469C>A
ENST00000615910.4:n.913C>A
ENST00000617185.4:c.946C>A
ENST00000618944.4:c.469C>A
ENST00000619186.4:c.469C>A
ENST00000619485.4:c.829C>A
ENST00000620739.4:c.829C>A
ENST00000622645.4:c.829C>A
ENST00000635293.1:c.829C>A
NM_001126112.2:c.946C>A
NM_001126113.2:c.946C>A
NM_001126114.2:c.946C>A
NM_001126115.1:c.550C>A
NM_001126116.1:c.550C>A
NM_001126117.1:c.550C>A
NM_001126118.1:c.829C>A
NM_001276695.1:c.829C>A
NM_001276696.1:c.829C>A
NM_001276697.1:c.469C>A
NM_001276698.1:c.469C>A
NM_001276699.1:c.469C>A
NM_001276760.1:c.829C>A
NM_001276761.1:c.829C>A
NM_001276695.2:c.829C>A
NM_001276696.2:c.829C>A
NM_001276697.2:c.469C>A
NM_001276698.2:c.469C>A
NM_001276699.2:c.469C>A
NM_001276760.2:c.829C>A
NM_001276761.2:c.829C>A
NM_000546.6:c.946C>A
NM_001126112.3:c.946C>A
NM_001126113.3:c.946C>A
NM_001126114.3:c.946C>A
NM_001126115.2:c.550C>A
NM_001126116.2:c.550C>A
NM_001126117.2:c.550C>A
NM_001126118.2:c.829C>A
NM_001276695.3:c.829C>A
NM_001276696.3:c.829C>A
NM_001276697.3:c.469C>A
NM_001276698.3:c.469C>A
NM_001276699.3:c.469C>A
NM_001276760.3:c.829C>A
NM_001276761.3:c.829C>A

Uncertain Significance

Met criteria codes 1
BP4
Not Met criteria codes 16
PS4 PS3 PS2 PS1 PP1 PP3 BA1 PM1 PM5 BS2 BS3 BS4 BS1 PM6 PM2 BP2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 (BP4). In summary, the clinical significance of TP53 c.946C>A (p.Pro316Thr) is uncertain for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: BP4.
Met criteria codes
BP4
Fortuno (PMID: 29775997) Align-GVGD Class: C0: Tolerated; Bayes-del: -0.0226052
Not Met criteria codes
PS4
Variant not found in the literature.
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
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
PM1
Not in a hotspot codon. Not found in cancerhotspots.
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
Not found in FLOSSIES database. No women 60+ years with no cancer reported by Ambry: Organization ID: 61756 or Color: Organization ID: One woman 60+ years with no cancer each reported by GeneDx: Organization ID: 26957 and Invitae: Organization ID: 500031, respectively.
BS3
Giacomelli (PMID: 30224644) Nutlin = -0.465915908940697; Giacomelli Toposide = 0.545706793016165; N/A in Kotler: (PMID: 29979965);Kato (PMID: 12826609) Transactivation assay = 12.9. no DNE + no LOF + non-functional transactivation= “No evidence”
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
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
One allele (European non-Finnish) present in gnomAD v3.1.1 (non-cancer). Allele frequency: 1/68042 = 0.00001470
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Approved on: 2021-04-05
Published on: 2021-09-24
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.