chr1-17018903-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_003000.3(SDHB):c.821A>T(p.Lys274Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,458 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. K274E) 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SDHB | NM_003000.3 | c.821A>T | p.Lys274Met | missense_variant | 8/8 | ENST00000375499.8 | |
SDHB | NM_001407361.1 | c.767A>T | p.Lys256Met | missense_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SDHB | ENST00000375499.8 | c.821A>T | p.Lys274Met | missense_variant | 8/8 | 1 | NM_003000.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251346Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135858
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460458Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 726642
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 06, 2023 | The p.K274M variant (also known as c.821A>T), located in coding exon 8 of the SDHB gene, results from an A to T substitution at nucleotide position 821. The lysine at codon 274 is replaced by methionine, an amino acid with 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. - |
Hereditary pheochromocytoma-paraganglioma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Jan 11, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at