rs377566366
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_003001.5(SDHC):c.20+3G>A variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.00000672 in 148,840 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)
Consequence
SDHC
NM_003001.5 splice_donor_region, intron
NM_003001.5 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.7638
2
Clinical Significance
Conservation
PhyloP100: 4.80
Genes affected
SDHC (HGNC:10682): (succinate dehydrogenase complex subunit C) This gene encodes one of four nuclear-encoded subunits that comprise succinate dehydrogenase, also known as mitochondrial complex II, a key enzyme complex of the tricarboxylic acid cycle and aerobic respiratory chains of mitochondria. The encoded protein is one of two integral membrane proteins that anchor other subunits of the complex, which form the catalytic core, to the inner mitochondrial membrane. There are several related pseudogenes for this gene on different chromosomes. Mutations in this gene have been associated with paragangliomas. Alternatively spliced transcript variants have been described. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.22).
BP6
?
Variant 1-161314428-G-A is Benign according to our data. Variant chr1-161314428-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 407050.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SDHC | NM_003001.5 | c.20+3G>A | splice_donor_region_variant, intron_variant | ENST00000367975.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SDHC | ENST00000367975.7 | c.20+3G>A | splice_donor_region_variant, intron_variant | 1 | NM_003001.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000672 AC: 1AN: 148840Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248624Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134416
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GnomAD4 exome Cov.: 30
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GnomAD4 genome ? AF: 0.00000672 AC: 1AN: 148840Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 72670
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Gastrointestinal stromal tumor;C1854336:Paragangliomas 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 24, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at