rs751247705
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4BP6_Very_StrongBS2
The NM_000368.5(TSC1):c.1808C>T(p.Pro603Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000044 in 1,614,064 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P603Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_000368.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC1 | NM_000368.5 | c.1808C>T | p.Pro603Leu | missense_variant | 15/23 | ENST00000298552.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC1 | ENST00000298552.9 | c.1808C>T | p.Pro603Leu | missense_variant | 15/23 | 1 | NM_000368.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152176Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000597 AC: 15AN: 251130Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135732
GnomAD4 exome AF: 0.0000438 AC: 64AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.0000481 AC XY: 35AN XY: 727246
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152176Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74346
ClinVar
Submissions by phenotype
Tuberous sclerosis 1 Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Dec 15, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2024 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 25, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2022 | TSC1: BS2 - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 07, 2019 | 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. - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Jul 05, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at