rs200973284
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_003000.3(SDHB):c.344G>T(p.Arg115Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R115G) has been classified as Uncertain significance.
Frequency
Consequence
NM_003000.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SDHB | NM_003000.3 | c.344G>T | p.Arg115Leu | missense_variant | 4/8 | ENST00000375499.8 | NP_002991.2 | |
SDHB | NM_001407361.1 | c.344G>T | p.Arg115Leu | missense_variant | 4/8 | NP_001394290.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SDHB | ENST00000375499.8 | c.344G>T | p.Arg115Leu | missense_variant | 4/8 | 1 | NM_003000.3 | ENSP00000364649.3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251458Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135910
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461806Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727210
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Pheochromocytoma;C0238198:Gastrointestinal stromal tumor;C1861848:Paragangliomas 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 07, 2023 | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SDHB protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals affected with SDHB-related conditions. This variant is present in population databases (rs200973284, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 115 of the SDHB protein (p.Arg115Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at