rs375883981
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_004168.4(SDHA):c.1794+3G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004168.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SDHA | NM_004168.4 | c.1794+3G>A | splice_region_variant, intron_variant | Intron 13 of 14 | ENST00000264932.11 | NP_004159.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SDHA | ENST00000264932.11 | c.1794+3G>A | splice_region_variant, intron_variant | Intron 13 of 14 | 1 | NM_004168.4 | ENSP00000264932.6 | |||
ENSG00000286001 | ENST00000651543.1 | n.*527+3G>A | splice_region_variant, intron_variant | Intron 12 of 23 | ENSP00000499215.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152224Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250688Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135542
GnomAD4 exome Cov.: 32
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152224Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74362
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
The c.1794+3G>A intronic variant results from a G to A substitution 3 nucleotides after coding exon 13 in the SDHA gene. This nucleotide position is not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Paragangliomas 5;C5700310:Mitochondrial complex II deficiency, nuclear type 1 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at