rs374450282

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_003001.5(SDHC):c.162C>A(p.Pro54Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000354 in 1,607,966 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 (★★). Synonymous variant affecting the same amino acid position (i.e. P54P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

SDHC
NM_003001.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.64

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 1-161328480-C-A is Benign according to our data. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161328480-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 465963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.64 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0000328 (5/152258) while in subpopulation SAS AF = 0.00104 (5/4828). AF 95% confidence interval is 0.000408. There are 0 homozygotes in GnomAd4. There are 2 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 5 Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDHC	NM_003001.5 link	c.162C>A	p.Pro54Pro	synonymous_variant	Exon 3 of 6	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.162C>A	p.Pro54Pro	synonymous_variant	Exon 3 of 6	1	NM_003001.5	ENSP00000356953.3		Q99643-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000994

AC:

AN:

251464

AF XY:

0.000132

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:

0.000326

GnomAD4 exome

AF:

0.0000357

AC:

AN:

1455708

Hom.:

Cov.:

AF XY:

0.0000524

AC XY:

AN XY:

724648

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33344

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.000488

AC:

AN:

86134

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1106400

Other (OTH)

AF:

0.000133

AC:

AN:

60188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41558

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00104

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Pheochromocytoma/paraganglioma syndrome 3

Benign:2

Mar 14, 2025

Myriad Genetics, Inc.

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:1

Apr 23, 2020

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. -

Gastrointestinal stromal tumor;C1854336:Pheochromocytoma/paraganglioma syndrome 3

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary pheochromocytoma-paraganglioma

Benign:1

Feb 05, 2024

All of Us Research Program, National Institutes of Health

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

-0.34

CADD

Benign

0.39

(source)

DANN

Benign

0.59

PhyloP100

-1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over