NM_000548.5:c.583A>G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_000548.5(TSC2):āc.583A>Gā(p.Ile195Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000266 in 1,613,972 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. I195M) has been classified as Uncertain significance.
Frequency
Consequence
NM_000548.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152220Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000437 AC: 11AN: 251496Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135922
GnomAD4 exome AF: 0.0000260 AC: 38AN: 1461752Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17AN XY: 727196
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152220Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74354
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
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TSC2: BP4, BS2 -
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Tuberous sclerosis 2 Benign:2
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Hereditary cancer-predisposing syndrome Benign:2
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. -
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TSC2-related disorder Uncertain:1
The TSC2 c.583A>G variant is predicted to result in the amino acid substitution p.Ile195Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0079% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Tuberous sclerosis syndrome Benign:1
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Lymphangiomyomatosis;C1846385:Isolated focal cortical dysplasia type II;C1860707:Tuberous sclerosis 2 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at