5-218351-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_004168.4(SDHA):c.-5C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,458,206 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 (★★).
Frequency
Consequence
NM_004168.4 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SDHA | NM_004168.4 | c.-5C>T | 5_prime_UTR_variant | Exon 1 of 15 | ENST00000264932.11 | NP_004159.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SDHA | ENST00000264932 | c.-5C>T | 5_prime_UTR_variant | Exon 1 of 15 | 1 | NM_004168.4 | ENSP00000264932.6 | |||
ENSG00000286001 | ENST00000651543.1 | n.-5C>T | non_coding_transcript_exon_variant | Exon 1 of 24 | ENSP00000499215.1 | |||||
ENSG00000286001 | ENST00000651543.1 | n.-5C>T | 5_prime_UTR_variant | Exon 1 of 24 | ENSP00000499215.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152188Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000629 AC: 7AN: 111366Hom.: 0 AF XY: 0.0000777 AC XY: 5AN XY: 64368
GnomAD4 exome AF: 0.0000107 AC: 14AN: 1305910Hom.: 0 Cov.: 31 AF XY: 0.0000109 AC XY: 7AN XY: 644432
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152296Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74468
ClinVar
Submissions by phenotype
Paragangliomas 5 Uncertain:2
This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. -
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not provided Uncertain:1
Has not been previously published as pathogenic or benign to our knowledge; In silico analysis predicts this variant does not impact splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change is unknown -
Hereditary cancer-predisposing syndrome Uncertain:1
The c.-5C>T variant is located in the 5' untranslated region (5’ UTR) of the SDHA gene. This variant results from a C to T substitution 5 bases upstream from the first translated codon. This nucleotide position is not conserved on limited sequence alignment. 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