rs757751865
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001406665.1(TSC2):c.3757G>A(p.Ala1253Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000726 in 1,610,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 7/7 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001406665.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.3883+6G>A | splice_region_variant, intron_variant | ENST00000219476.9 | NP_000539.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.3883+6G>A | splice_region_variant, intron_variant | 5 | NM_000548.5 | ENSP00000219476.3 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152212Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000644 AC: 16AN: 248400Hom.: 0 AF XY: 0.0000445 AC XY: 6AN XY: 134966
GnomAD4 exome AF: 0.0000747 AC: 109AN: 1458520Hom.: 0 Cov.: 31 AF XY: 0.0000689 AC XY: 50AN XY: 725666
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152212Hom.: 0 Cov.: 34 AF XY: 0.0000538 AC XY: 4AN XY: 74356
ClinVar
Submissions by phenotype
Tuberous sclerosis 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 03, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 28, 2020 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jun 05, 2024 | The frequency of this variant in the general population (http://gnomad.broadinstitute.org) is higher than would generally be expected for pathogenic variants in this gene. This nucleotide position exhibits low evolutionary conservation. - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Sep 16, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at