1-161340662-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_003001.5(SDHC):c.241+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,612,626 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SDHC
NM_003001.5 splice_region, intron

Scores

Splicing: ADA: 0.00003567

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.542

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

hereditary pheochromocytoma-paraganglioma
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
pheochromocytoma/paraganglioma syndrome 3
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
Carney-Stratakis syndrome
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
gastrointestinal stromal tumor
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
renal cell carcinoma
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
Cowden disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
mitochondrial disease
Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

SDHC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 1-161340662-A-G is Benign according to our data. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161340662-A-G is described in CliVar as Likely_benign. Clinvar id is 239450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDHC	NM_003001.5 link	c.241+7A>G		splice_region_variant, intron_variant	Intron 4 of 5	ENST00000367975.7	NP_002992.1	Q99643-1A0A0S2Z4B7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDHC	ENST00000367975.7 link	c.241+7A>G		splice_region_variant, intron_variant	Intron 4 of 5	1	NM_003001.5	ENSP00000356953.3		Q99643-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

248934

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460504

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726676

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110790

Other (OTH)

AF:

0.00

AC:

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41412

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Pheochromocytoma/paraganglioma syndrome 3

Benign:1

Mar 14, 2025

Myriad Genetics, Inc.

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing. -

Gastrointestinal stromal tumor;C1854336:Pheochromocytoma/paraganglioma syndrome 3

Benign:1

Dec 04, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000036

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over