rs752701561
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7
The NM_000546.6(TP53):c.895C>T(p.Leu299=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L299L) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TP53
NM_000546.6 synonymous
NM_000546.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.677
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 17-7673725-G-A is Benign according to our data. Variant chr17-7673725-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 414039.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.677 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TP53 | NM_000546.6 | c.895C>T | p.Leu299= | synonymous_variant | 8/11 | ENST00000269305.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TP53 | ENST00000269305.9 | c.895C>T | p.Leu299= | synonymous_variant | 8/11 | 1 | NM_000546.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
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31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251490Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135922
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1AN: 1461892Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727248
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome ? Cov.: 31
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Li-Fraumeni syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 20, 2020 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at