VCV000165182.45 - ClinVar

NM_003001.5(SDHC):c.354T>C (p.Phe118=)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(13)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_003001.5(SDHC):c.354T>C (p.Phe118=)

Variation ID: 165182 Accession: VCV000165182.45

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1q23.3 1: 161356789 (GRCh38) [ NCBI UCSC ] 1: 161326579 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Feb 2, 2015	Dec 22, 2024	Feb 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_003001.5:c.354T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002992.1:p.Phe118=	synonymous
NM_001035511.3:c.242-5540T>C		intron variant
NM_001035512.3:c.252T>C	NP_001030589.1:p.Phe84=	synonymous
NM_001035513.3:c.195T>C	NP_001030590.1:p.Phe65=	synonymous
NM_001278172.3:c.140-5540T>C		intron variant
NM_001407115.1:c.474T>C	NP_001394044.1:p.Phe158=	synonymous
NM_001407116.1:c.297T>C	NP_001394045.1:p.Phe99=	synonymous
NM_001407117.1:c.291T>C	NP_001394046.1:p.Phe97=	synonymous
NM_001407118.1:c.246T>C	NP_001394047.1:p.Phe82=	synonymous
NM_001407119.1:c.243T>C	NP_001394048.1:p.Phe81=	synonymous
NM_001407120.1:c.243T>C	NP_001394049.1:p.Phe81=	synonymous
NM_001407121.1:c.185-5540T>C		intron variant
NR_103459.3:n.406T>C		non-coding transcript variant
NC_000001.11:g.161356789T>C
NC_000001.10:g.161326579T>C
NG_012767.1:g.47414T>C
LRG_317:g.47414T>C
LRG_317t1:c.354T>C	LRG_317p1:p.Phe118=

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000001.11:161356788:T:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00379 (C)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00103

Exome Aggregation Consortium (ExAC) 0.00133

1000 Genomes Project 0.00379

Trans-Omics for Precision Medicine (TOPMed) 0.00441

1000 Genomes Project 30x 0.00453

The Genome Aggregation Database (gnomAD) 0.00454

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00561

Links

ClinGen: CA011442 dbSNP: rs61733156 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
SDHC		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	879	921

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Benign/Likely benign (5)	criteria provided, multiple submitters, no conflicts	Aug 15, 2023	RCV000151829.18
Hereditary cancer-predisposing syndrome	Benign (1)	criteria provided, single submitter	Nov 20, 2015	RCV000162606.7
not provided	Benign (3)	criteria provided, multiple submitters, no conflicts	Jan 1, 2024	RCV000589493.24
Gastrointestinal stromal tumor Paragangliomas 3	Benign (1)	criteria provided, single submitter	Feb 1, 2024	RCV001079839.10
SDHC-related disorder	Benign (1)	no assertion criteria provided	Jun 12, 2019	RCV003917480.2
Paragangliomas 3	Benign (2)	criteria provided, multiple submitters, no conflicts	Jul 7, 2023	RCV003315940.4

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (Nov 05, 2013)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000200300.5 First in ClinVar: Feb 02, 2015 Last updated: May 03, 2018	Number of individuals with the variant: 1
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Paragangliomas 3 Gastrointestinal stromal tumor Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000287801.9 First in ClinVar: Jul 01, 2016 Last updated: Feb 28, 2024
Benign (Nov 20, 2015)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000213033.7 First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024	Comment: This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more) This alteration is classified as 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. (less)
Benign (May 25, 2016)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000698138.1 First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018	Comment: Variant summary: The SDHC c.354T>C (p.Phe118Phe) variant causes a synonymous change involving a non-conserved nucleotide with 5/5 splice prediction tools predicting no significant effect on … (more) Variant summary: The SDHC c.354T>C (p.Phe118Phe) variant causes a synonymous change involving a non-conserved nucleotide with 5/5 splice prediction tools predicting no significant effect on splicing and the creation of two ESE binding sites, however, these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 162/121412 (1 homozygote, 1/749, frequency: 0.001334), predominantly observed in the African cohort, 159/10406 (1 homozygote, 1/65, frequency: 0.01528), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic SDHC variant of 1/5000000 (0.0000002). Therefore, suggesting this variant is a common polymorphism found in population(s) of African origin. In addition, reputable clinical laboratories cite the variant as "benign." Therefore, the variant of interest is classified as Benign. (less)
Likely benign (Nov 30, 2017)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	not specified Affected status: yes Allele origin: germline	GeneDx Accession: SCV000724256.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018	Comment: This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more) This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
Benign (Feb 13, 2018)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process) Method: clinical testing	Not Provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000886092.1 First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018
Benign (Sep 28, 2021)	criteria provided, single submitter (Quest Diagnostics criteria) Method: clinical testing	not specified Affected status: unknown Allele origin: unknown	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV000888620.3 First in ClinVar: Mar 13, 2019 Last updated: Dec 31, 2022
Benign (Apr 25, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: no Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV002066138.1 First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022
Benign (Jul 07, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Paragangliomas 3 Affected status: yes Allele origin: germline	KCCC/NGS Laboratory, Kuwait Cancer Control Center Accession: SCV004015421.1 First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023
Benign (Aug 15, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital Accession: SCV002552554.4 First in ClinVar: Jul 30, 2022 Last updated: Aug 18, 2023
Benign (Oct 03, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Paragangliomas 3 Affected status: unknown Allele origin: germline	Color Diagnostics, LLC DBA Color Health Accession: SCV004362295.1 First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024
Benign (Jan 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV004700891.9 First in ClinVar: Mar 10, 2024 Last updated: Dec 22, 2024	Comment: SDHC: BP4, BP7, BS1, BS2 Number of individuals with the variant: 1
Benign (Jun 12, 2019)	no assertion criteria provided Method: clinical testing	SDHC-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004732357.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Comment:

This alteration is classified as 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.

Comment:

Variant summary: The SDHC c.354T>C (p.Phe118Phe) variant causes a synonymous change involving a non-conserved nucleotide with 5/5 splice prediction tools predicting no significant effect on splicing and the creation of two ESE binding sites, however, these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 162/121412 (1 homozygote, 1/749, frequency: 0.001334), predominantly observed in the African cohort, 159/10406 (1 homozygote, 1/65, frequency: 0.01528), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic SDHC variant of 1/5000000 (0.0000002). Therefore, suggesting this variant is a common polymorphism found in population(s) of African origin. In addition, reputable clinical laboratories cite the variant as "benign." Therefore, the variant of interest is classified as Benign.

Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs61733156 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jan 13, 2025

ClinVar Genomic variation as it relates to human health

NM_003001.5(SDHC):c.354T>C (p.Phe118=)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs61733156 ...