rs764843485
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_003000.3(SDHB):āc.164A>Gā(p.Lys55Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,202 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K55T) 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 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SDHB | NM_003000.3 | c.164A>G | p.Lys55Arg | missense_variant | 2/8 | ENST00000375499.8 | |
SDHB | NM_001407361.1 | c.164A>G | p.Lys55Arg | missense_variant | 2/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SDHB | ENST00000375499.8 | c.164A>G | p.Lys55Arg | missense_variant | 2/8 | 1 | NM_003000.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251386Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135874
GnomAD4 exome Cov.: 32
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74366
ClinVar
Submissions by phenotype
Pheochromocytoma;C0238198:Gastrointestinal stromal tumor;C1861848:Paragangliomas 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 10, 2023 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 583392). This variant has not been reported in the literature in individuals affected with SDHB-related conditions. This variant is present in population databases (rs764843485, gnomAD 0.007%). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 55 of the SDHB protein (p.Lys55Arg). - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 02, 2022 | The p.K55R variant (also known as c.164A>G), located in coding exon 2 of the SDHB gene, results from an A to G substitution at nucleotide position 164. The lysine at codon 55 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. 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