chr9-132896623-C-T
Variant summary
Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_000368.5(TSC1):c.3107G>A(p.Gly1036Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. G1036K) has been classified as Uncertain significance.
Frequency
Consequence
NM_000368.5 missense
Scores
Clinical Significance
Conservation
Publications
- tuberous sclerosisInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- tuberous sclerosis 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, PanelApp Australia, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
- lung lymphangioleiomyomatosisInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
- tuberous sclerosis complexInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Benign. The variant received -7 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TSC1 | ENST00000298552.9 | c.3107G>A | p.Gly1036Glu | missense_variant | Exon 23 of 23 | 1 | NM_000368.5 | ENSP00000298552.3 | ||
TSC1 | ENST00000490179.4 | c.3107G>A | p.Gly1036Glu | missense_variant | Exon 24 of 24 | 3 | ENSP00000495533.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD2 exomes AF: 0.00000401 AC: 1AN: 249664 AF XY: 0.00000739 show subpopulations
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461532Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727040 show subpopulations
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
TSC1: BP4 -
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Tuberous sclerosis 1 Benign:2
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TSC1-related disorder Uncertain:1
The TSC1 c.3107G>A variant is predicted to result in the amino acid substitution p.Gly1036Glu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Hereditary cancer-predisposing syndrome Benign: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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at