chr16-2080195-A-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_000548.5(TSC2):c.3428A>T(p.Asp1143Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,460,598 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D1143E) has been classified as Uncertain significance.
Frequency
Consequence
NM_000548.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.3428A>T | p.Asp1143Val | missense_variant | 30/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.3428A>T | p.Asp1143Val | missense_variant | 30/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250350Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135698
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1460598Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 726592
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Tuberous sclerosis 2 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 09, 2023 | The p.D1143V variant (also known as c.3428A>T), located in coding exon 29 of the TSC2 gene, results from an A to T substitution at nucleotide position 3428. The aspartic acid at codon 1143 is replaced by valine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 26, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at