rs200749357
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS2
The NM_000368.5(TSC1):āc.830T>Cā(p.Val277Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000619 in 1,614,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000368.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TSC1 | NM_000368.5 | c.830T>C | p.Val277Ala | missense_variant | 9/23 | ENST00000298552.9 | NP_000359.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TSC1 | ENST00000298552.9 | c.830T>C | p.Val277Ala | missense_variant | 9/23 | 1 | NM_000368.5 | ENSP00000298552.3 | ||
TSC1 | ENST00000490179.4 | c.830T>C | p.Val277Ala | missense_variant | 10/24 | 3 | ENSP00000495533.2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152218Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251438Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135894
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727246
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152336Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74496
ClinVar
Submissions by phenotype
Tuberous sclerosis syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | May 09, 2024 | This missense variant replaces valine with alanine at codon 277 of the TSC1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TSC1-related disorders in the literature. This variant has been identified in 2/282846 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Tuberous sclerosis 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 18, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 02, 2020 | 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