rs45448791
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_000548.5(TSC2):c.4313G>A(p.Arg1438Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000994 in 1,609,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1438W) 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 -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.4313G>A | p.Arg1438Gln | missense_variant | 34/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.4313G>A | p.Arg1438Gln | missense_variant | 34/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152248Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000168 AC: 4AN: 238686Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 130884
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1457006Hom.: 0 Cov.: 33 AF XY: 0.00000966 AC XY: 7AN XY: 724854
GnomAD4 genome ? AF: 0.00000656 AC: 1AN: 152366Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74510
ClinVar
Submissions by phenotype
Tuberous sclerosis 2 Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 20, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Tuberous sclerosis syndrome Uncertain:1Other:1
not provided, no classification provided | curation | Tuberous sclerosis database (TSC2) | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Nov 30, 2023 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 19, 2019 | The p.R1438Q variant (also known as c.4313G>A), located in coding exon 33 of the TSC2 gene, results from a G to A substitution at nucleotide position 4313. The arginine at codon 1438 is replaced by glutamine, an amino acid with highly similar properties. This variant was reportedly de novo in an individual with tuberous sclerosis (Roberts PS et al. J. Med. Genet., 2004 May;41:e69). This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at