9-132921913-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 6P and 5B. PM1PM5PP2PP3BP6BS2
The NM_000368.5(TSC1):c.569G>A(p.Arg190His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R190C) has been classified as Likely benign.
Frequency
Consequence
NM_000368.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC1 | NM_000368.5 | c.569G>A | p.Arg190His | missense_variant | 7/23 | ENST00000298552.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC1 | ENST00000298552.9 | c.569G>A | p.Arg190His | missense_variant | 7/23 | 1 | NM_000368.5 | P4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251344Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135834
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461872Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727244
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Tuberous sclerosis 1 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 11, 2023 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 26, 2023 | The p.R190H variant (also known as c.569G>A), located in coding exon 5 of the TSC1 gene, results from a G to A substitution at nucleotide position 569. The arginine at codon 190 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at