rs3813632
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_003001.5(SDHC):c.*123C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 1,607,096 control chromosomes in the GnomAD database, including 6,154 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.085 ( 645 hom., cov: 31)
Exomes 𝑓: 0.075 ( 5509 hom. )
Consequence
SDHC
NM_003001.5 3_prime_UTR
NM_003001.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.135
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 1-161362556-C-G is Benign according to our data. Variant chr1-161362556-C-G is described in ClinVar as [Benign]. Clinvar id is 286523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SDHC | NM_003001.5 | c.*123C>G | 3_prime_UTR_variant | 6/6 | ENST00000367975.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SDHC | ENST00000367975.7 | c.*123C>G | 3_prime_UTR_variant | 6/6 | 1 | NM_003001.5 | P1 | ||
SDHC | ENST00000342751.8 | c.*16C>G | 3_prime_UTR_variant | 5/5 | 1 | ||||
SDHC | ENST00000470743.5 | c.*634C>G | 3_prime_UTR_variant, NMD_transcript_variant | 7/7 | 5 | ||||
SDHC | ENST00000513009.5 | downstream_gene_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0845 AC: 12852AN: 152024Hom.: 645 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
12852
AN:
152024
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0932 AC: 22435AN: 240726Hom.: 1387 AF XY: 0.0958 AC XY: 12523AN XY: 130734
GnomAD3 exomes
AF:
AC:
22435
AN:
240726
Hom.:
AF XY:
AC XY:
12523
AN XY:
130734
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0749 AC: 108921AN: 1454954Hom.: 5509 Cov.: 35 AF XY: 0.0778 AC XY: 56259AN XY: 723446
GnomAD4 exome
AF:
AC:
108921
AN:
1454954
Hom.:
Cov.:
35
AF XY:
AC XY:
56259
AN XY:
723446
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0845 AC: 12859AN: 152142Hom.: 645 Cov.: 31 AF XY: 0.0884 AC XY: 6572AN XY: 74350
GnomAD4 genome
?
AF:
AC:
12859
AN:
152142
Hom.:
Cov.:
31
AF XY:
AC XY:
6572
AN XY:
74350
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 25, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Hereditary pheochromocytoma-paraganglioma Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at