rs747613240
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 4P and 13B. PM1PM5BP4BP6_Very_StrongBS2
The NM_000548.5(TSC2):c.4510C>T(p.Leu1504Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,613,232 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. L1504H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000548.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.4510C>T | p.Leu1504Phe | missense_variant | 35/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.4510C>T | p.Leu1504Phe | missense_variant | 35/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152224Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000959 AC: 24AN: 250346Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135756
GnomAD4 exome AF: 0.0000315 AC: 46AN: 1461008Hom.: 0 Cov.: 33 AF XY: 0.0000261 AC XY: 19AN XY: 726820
GnomAD4 genome AF: 0.0000920 AC: 14AN: 152224Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74366
ClinVar
Submissions by phenotype
Tuberous sclerosis 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 16, 2022 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at