Variant rs75726722 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_003001.5(SDHC):c.20+11_20+12dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0822 in 1,613,892 control chromosomes in the GnomAD database, including 7,980 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1434 hom., cov: 30)

Exomes 𝑓: 0.078 ( 6546 hom. )

Consequence

SDHC
NM_003001.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -0.656

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-161314434-A-AGT is Benign according to our data. Variant chr1-161314434-A-AGT is described in ClinVar as [Benign]. Clinvar id is 44647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 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.20+11_20+12dup		intron_variant		ENST00000367975.7	NP_002992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDHC	ENST00000367975.7 linkuse as main transcript	c.20+11_20+12dup		intron_variant		1	NM_003001.5	ENSP00000356953	P1	Q99643-1

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17935

AN:

152046

Hom.:

1431

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0703

Gnomad ASJ

AF:

0.0282

Gnomad EAS

AF:

0.208

Gnomad SAS

AF:

0.187

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0644

Gnomad OTH

AF:

0.0946

GnomAD3 exomes

AF:

0.0998

AC:

25060

AN:

251148

Hom.:

1737

AF XY:

0.100

AC XY:

13601

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.224

Gnomad AMR exome

AF:

0.0523

Gnomad ASJ exome

AF:

0.0281

Gnomad EAS exome

AF:

0.196

Gnomad SAS exome

AF:

0.184

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.0649

Gnomad OTH exome

AF:

0.0827

GnomAD4 exome

AF:

0.0784

AC:

114671

AN:

1461728

Hom.:

6546

Cov.:

AF XY:

0.0811

AC XY:

58942

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.224

Gnomad4 AMR exome

AF:

0.0539

Gnomad4 ASJ exome

AF:

0.0300

Gnomad4 EAS exome

AF:

0.260

Gnomad4 SAS exome

AF:

0.181

Gnomad4 FIN exome

AF:

0.0964

Gnomad4 NFE exome

AF:

0.0608

Gnomad4 OTH exome

AF:

0.0820

GnomAD4 genome

AF:

0.118

AC:

17957

AN:

152164

Hom.:

1434

Cov.:

AF XY:

0.121

AC XY:

8973

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.219

Gnomad4 AMR

AF:

0.0701

Gnomad4 ASJ

AF:

0.0282

Gnomad4 EAS

AF:

0.209

Gnomad4 SAS

AF:

0.187

Gnomad4 FIN

AF:

0.104

Gnomad4 NFE

AF:

0.0644

Gnomad4 OTH

AF:

0.0936

Alfa

AF:

0.0810

Hom.:

166

Bravo

AF:

0.116

Asia WGS

AF:

0.202

AC:

699

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 25, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	May 25, 2016	Variant summary: The SDHC c.20+11_20+12dupTG is an intronic variant at a position not widely known to affect splicing. One in silico tool (MutationTaster) predicts a damaging outcome for this variant. 4/5 splice prediction tools predict no significant change to the normal splicing. This variant was found in 12727/120920 control chromosomes (including 891 homozygotes) at a frequency of 0.1052514, which is approximately 673609 times the estimated maximal expected allele frequency of a pathogenic SDHC variant (0.0000002), suggesting this variant is a common benign polymorphism. In addition, one clinical diagnostic laboratory classified this variant as benign. Taken together, based on the allele frequency in the general population, this variant is classified as Benign. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 05, 2013	20+11_20+12dupTG in intron 1 of SDHC: This variant has been identified in 15% ( 63/420) of patients with hereditary paraganglioma and in 6% (11/200) of controls (Burnichon 2009). This variant is also annotated as a common polymorphism in db SNP and but has been identified in 6% (516/8254) of European American chromosome s and 21% (889/4266) of African American chromosomes by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS/; dbSNP rs27118366). This variant i s located in the 5' splice region and computational tools do not suggest an impa ct to splicing. However, this information is not predictive enough to rule out p athogenicity. In summary, these data support that the 20+11_20+12dupTG variant i s benign based on frequency data. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Charcot-Marie-Tooth disease type 4E

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Roussy-Lévy syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Pheochromocytoma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Gastrointestinal stromal tumor;C1854336:Paragangliomas 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Hereditary cancer-predisposing syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 08, 2015

This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Charcot-Marie-Tooth disease, type I

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Charcot-Marie-Tooth, Intermediate

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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