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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.135

Variant links:

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]

SDHC links:

SDHC (HGNC:):

SDHC links:

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	Protein	UniProt
SDHC	NM_003001.5 linkuse as main transcript	c.*123C>G		3_prime_UTR_variant	6/6	ENST00000367975.7	NP_002992.1	Q99643-1A0A0S2Z4B7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDHC	ENST00000367975.7 linkuse as main transcript	c.*123C>G		3_prime_UTR_variant	6/6	1	NM_003001.5	ENSP00000356953.3		Q99643-1

Frequencies

GnomAD3 genomes

AF:

0.0845

AC:

12852

AN:

152024

Hom.:

645

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0609

Gnomad ASJ

AF:

0.0282

Gnomad EAS

AF:

0.207

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0637

Gnomad OTH

AF:

0.0726

GnomAD3 exomes

AF:

0.0932

AC:

22435

AN:

240726

Hom.:

1387

AF XY:

0.0958

AC XY:

12523

AN XY:

130734

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.0597

Gnomad ASJ exome

AF:

0.0282

Gnomad EAS exome

AF:

0.196

Gnomad SAS exome

AF:

0.182

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.0651

Gnomad OTH exome

AF:

0.0789

GnomAD4 exome

AF:

0.0749

AC:

108921

AN:

1454954

Hom.:

5509

Cov.:

AF XY:

0.0778

AC XY:

56259

AN XY:

723446

show subpopulations

Gnomad4 AFR exome

AF:

0.105

Gnomad4 AMR exome

AF:

0.0612

Gnomad4 ASJ exome

AF:

0.0299

Gnomad4 EAS exome

AF:

0.259

Gnomad4 SAS exome

AF:

0.178

Gnomad4 FIN exome

AF:

0.0963

Gnomad4 NFE exome

AF:

0.0602

Gnomad4 OTH exome

AF:

0.0732

GnomAD4 genome

AF:

0.0845

AC:

12859

AN:

152142

Hom.:

645

Cov.:

AF XY:

0.0884

AC XY:

6572

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.0610

Gnomad4 ASJ

AF:

0.0282

Gnomad4 EAS

AF:

0.207

Gnomad4 SAS

AF:

0.183

Gnomad4 FIN

AF:

0.104

Gnomad4 NFE

AF:

0.0637

Gnomad4 OTH

AF:

0.0718

Alfa

AF:

0.0684

Hom.:

Bravo

AF:

0.0786

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Feb 25, 2016

- -

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.8

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over