chr9-132897613-G-GAAA
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1
The NM_000368.5(TSC1):c.2626-6_2626-4dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000368.5 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TSC1 | ENST00000298552.9 | c.2626-4_2626-3insTTT | splice_region_variant, intron_variant | Intron 20 of 22 | 1 | NM_000368.5 | ENSP00000298552.3 | |||
TSC1 | ENST00000490179.4 | c.2626-4_2626-3insTTT | splice_region_variant, intron_variant | Intron 21 of 23 | 3 | ENSP00000495533.2 |
Frequencies
GnomAD3 genomes AF: 0.0133 AC: 1380AN: 103968Hom.: 42 Cov.: 0
GnomAD3 exomes AF: 0.0565 AC: 5864AN: 103824Hom.: 78 AF XY: 0.0562 AC XY: 3223AN XY: 57384
GnomAD4 exome AF: 0.0469 AC: 57600AN: 1229252Hom.: 171 Cov.: 0 AF XY: 0.0468 AC XY: 28562AN XY: 610466
GnomAD4 genome AF: 0.0132 AC: 1377AN: 103970Hom.: 41 Cov.: 0 AF XY: 0.0127 AC XY: 618AN XY: 48524
ClinVar
Submissions by phenotype
not specified Benign:4
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not provided Benign:2
Variant summary: The TSC1 c.2626-6_2626-4dupTTT variant involves the duplication of three nucleotides in an intronic region. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 2772/80186 control chromosomes (50 homozygotes) at a frequency of 0.0345696, which greatly exceeds the estimated maximal expected allele frequency of a pathogenic TSC1 variant (0.000025), suggesting this variant is likely a benign polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign. -
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Tuberous sclerosis 1 Benign:2
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Tuberous sclerosis syndrome Uncertain:1
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Isolated focal cortical dysplasia type II Uncertain:1
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Hereditary cancer-predisposing syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at