chr9-132906011-C-G
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2
The NM_000368.5(TSC1):c.1567G>C(p.Ala523Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,614,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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. A523T) 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 -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC1 | NM_000368.5 | c.1567G>C | p.Ala523Pro | missense_variant | 15/23 | ENST00000298552.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC1 | ENST00000298552.9 | c.1567G>C | p.Ala523Pro | missense_variant | 15/23 | 1 | NM_000368.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152086Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251290Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135830
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461862Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727232
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74398
ClinVar
Submissions by phenotype
Tuberous sclerosis 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
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 | Sep 14, 2018 | 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. - |
Tuberous sclerosis syndrome Other:1
not provided, no classification provided | curation | Tuberous sclerosis database (TSC1) | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at