rs761381438
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_003001.5(SDHC):c.24C>A(p.His8Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,612,766 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H8N) has been classified as Uncertain significance.
Frequency
Consequence
NM_003001.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SDHC | NM_003001.5 | c.24C>A | p.His8Gln | missense_variant | 2/6 | ENST00000367975.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SDHC | ENST00000367975.7 | c.24C>A | p.His8Gln | missense_variant | 2/6 | 1 | NM_003001.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248994Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134780
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460620Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 2AN XY: 726736
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74316
ClinVar
Submissions by phenotype
Gastrointestinal stromal tumor;C1854336:Paragangliomas 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 21, 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 465967). This variant has not been reported in the literature in individuals affected with SDHC-related conditions. This variant is present in population databases (rs761381438, gnomAD 0.007%). This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 8 of the SDHC protein (p.His8Gln). - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 24, 2019 | The p.H8Q variant (also known as c.24C>A), located in coding exon 2 of the SDHC gene, results from a C to A substitution at nucleotide position 24. The histidine at codon 8 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. 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