5-218355-CAT-C
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_004168.4(SDHA):c.1_2delAT(p.Met1fs) variant causes a frameshift, start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Consequence
NM_004168.4 frameshift, start_lost
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SDHA | NM_004168.4 | c.1_2delAT | p.Met1fs | frameshift_variant, start_lost | Exon 1 of 15 | ENST00000264932.11 | NP_004159.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SDHA | ENST00000264932.11 | c.1_2delAT | p.Met1fs | frameshift_variant, start_lost | Exon 1 of 15 | 1 | NM_004168.4 | ENSP00000264932.6 | ||
ENSG00000286001 | ENST00000651543.1 | n.1_2delAT | non_coding_transcript_exon_variant | Exon 1 of 24 | ENSP00000499215.1 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Initiation codon variant in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge -
Paragangliomas 5 Pathogenic:1
The SDHA c.1_2del; p.Met1? change results in a deletion of two nucleotides at positions 1-2 of exon 1 of the SDHA gene. This results in loss of the initiation codon in a gene for which loss-of-function is a known mechanism of disease. The closest in-frame start codon is codon 114. Different nucleotide changes that also disrupt the initiation codon have been reported in individuals with clinical features of hereditary paraganglioma- pheochromocytoma syndrome (PMID: 26722403, 28384794, 31413764). This variant is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.