NM_000548.5:c.5389A>C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_000548.5(TSC2):āc.5389A>Cā(p.Ile1797Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict 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. I1797M) has been classified as Likely benign.
Frequency
Consequence
NM_000548.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.5389A>C | p.Ile1797Leu | missense_variant | Exon 42 of 42 | 5 | NM_000548.5 | ENSP00000219476.3 | ||
PKD1 | ENST00000262304.9 | c.*1152T>G | downstream_gene_variant | 1 | NM_001009944.3 | ENSP00000262304.4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 33
GnomAD4 exome Cov.: 33
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74314
ClinVar
Submissions by phenotype
Tuberous sclerosis 2 Benign:2
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Isolated focal cortical dysplasia type II Uncertain:1
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Hereditary cancer-predisposing syndrome Uncertain:1
The c.5389A>C (p.I1797L) alteration is located in exon 42 (coding exon 41) of the TSC2 gene. This alteration results from a A to C substitution at nucleotide position 5389, causing the isoleucine (I) at amino acid position 1797 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not specified Benign:1
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at