chr16-2079369-C-T
Variant summary
Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_000548.5(TSC2):c.3225C>T(p.Thr1075Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000769 in 1,612,778 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T1075T) has been classified as Likely benign.
Frequency
Consequence
NM_000548.5 synonymous
Scores
Clinical Significance
Conservation
Publications
- tuberous sclerosisInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- tuberous sclerosis 2Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Ambry Genetics
- 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 -17 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152142Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000400 AC: 10AN: 250144 AF XY: 0.0000737 show subpopulations
GnomAD4 exome AF: 0.0000808 AC: 118AN: 1460636Hom.: 0 Cov.: 31 AF XY: 0.0000826 AC XY: 60AN XY: 726600 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152142Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74294 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Tuberous sclerosis 2 Benign:4
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This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -
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not provided Benign:2
This variant is associated with the following publications: (PMID: 18854862, 26071483) -
TSC2: BP4, BP7 -
Tuberous sclerosis syndrome Benign:1Other:1
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TSC2-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
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