rs766093661
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PP3_ModerateBS2
The NM_000548.5(TSC2):c.5234G>A(p.Arg1745His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,612,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000548.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152196Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000800 AC: 2AN: 249876Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135582
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1460278Hom.: 0 Cov.: 34 AF XY: 0.0000193 AC XY: 14AN XY: 726432
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152196Hom.: 0 Cov.: 34 AF XY: 0.0000538 AC XY: 4AN XY: 74350
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
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This variant is associated with the following publications: (PMID: 28191889) -
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
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. -
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Tuberous sclerosis 2 Benign:2
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Tuberous sclerosis syndrome Uncertain:1
This missense variant replaces arginine with histidine at codon 1745 of the TSC2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TSC2-related disorders in the literature. This variant has been identified in 2/249876 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at