rs17113461

Variant names:

• chr11-112095773-A-G
• rs17113461
• NM_003002.4:c.*803A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003002.4(SDHD):​c.*803A>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 0.08 in 205,586 control chromosomes in the GnomAD database, including 2,317 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (2219 hom., cov: 33)
  • Exomes 𝑓: 0.024 (98 hom.)
• Consequence: SDHD NM_003002.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0710
• Publications: 5 publications found

Genes affected

SDHD (HGNC:10683): (succinate dehydrogenase complex subunit D) This gene encodes a member of complex II of the respiratory chain, which is responsible for the oxidation of succinate. The encoded protein is one of two integral membrane proteins anchoring the complex to the matrix side of the mitochondrial inner membrane. Mutations in this gene are associated with the formation of tumors, including hereditary paraganglioma. Transmission of disease occurs almost exclusively through the paternal allele, suggesting that this locus may be maternally imprinted. There are pseudogenes for this gene on chromosomes 1, 2, 3, 7, and 18. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2013]

SDHD Gene-Disease associations (from GenCC):

• hereditary pheochromocytoma-paraganglioma

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• pheochromocytoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• pheochromocytoma/paraganglioma syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• Carney-Stratakis syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
• mitochondrial complex II deficiency, nuclear type 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• renal cell carcinoma

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• mitochondrial complex 2 deficiency, nuclear type 3

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• mitochondrial complex II deficiency

  Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
• Cowden disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• intestinal cancer

  Inheritance: AD Classification: LIMITED Submitted by: G2P
• mitochondrial disease

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ENSG00000255292 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 11-112095773-A-G is Benign according to our data. Variant chr11-112095773-A-G is described in ClinVar as Benign. ClinVar VariationId is 44649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003002.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDHD	NM_003002.4	MANE Select	c.*803A>G		3_prime_UTR	Exon 4 of 4	NP_002993.1
	SDHD	NR_077060.2		n.1372A>G		non_coding_transcript_exon	Exon 5 of 5
	SDHD	NM_001276506.2		c.*981A>G		3_prime_UTR	Exon 5 of 5	NP_001263435.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDHD	ENST00000375549.8	TSL:1 MANE Select	c.*803A>G		3_prime_UTR	Exon 4 of 4	ENSP00000364699.3
	ENSG00000255292	ENST00000532699.1	TSL:3	n.314+6762A>G		intron	N/A	ENSP00000456434.1
	SDHD	ENST00000714090.1		n.*1080A>G		non_coding_transcript_exon	Exon 4 of 4	ENSP00000519381.1

Frequencies

GnomAD3 genomes AF: 0.0992 AC: 15096 AN: 152108 Hom.: 2190 Cov.: 33

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0456

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.00307

Gnomad SAS AF: 0.00496

Gnomad FIN AF: 0.00490

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.0765

GnomAD4 exome AF: 0.0241 AC: 1285 AN: 53360 Hom.: 98 Cov.: 0 AF XY: 0.0232 AC XY: 576 AN XY: 24838

African (AFR) AF: 0.271 AC: 624 AN: 2306

American (AMR) AF: 0.0442 AC: 67 AN: 1516

Ashkenazi Jewish (ASJ) AF: 0.0102 AC: 36 AN: 3526

East Asian (EAS) AF: 0.000398 AC: 3 AN: 7536

South Asian (SAS) AF: 0.00433 AC: 2 AN: 462

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38

Middle Eastern (MID) AF: 0.0311 AC: 10 AN: 322

European-Non Finnish (NFE) AF: 0.0107 AC: 354 AN: 33210

Other (OTH) AF: 0.0425 AC: 189 AN: 4444

GnomAD4 genome AF: 0.0996 AC: 15168 AN: 152226 Hom.: 2219 Cov.: 33 AF XY: 0.0969 AC XY: 7215 AN XY: 74452

African (AFR) AF: 0.322 AC: 13348 AN: 41490

American (AMR) AF: 0.0456 AC: 697 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3470

East Asian (EAS) AF: 0.00308 AC: 16 AN: 5194

South Asian (SAS) AF: 0.00455 AC: 22 AN: 4832

European-Finnish (FIN) AF: 0.00490 AC: 52 AN: 10610

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0116 AC: 791 AN: 68020

Other (OTH) AF: 0.0757 AC: 160 AN: 2114

Alfa AF: 0.0492 Hom.: 998

Bravo AF: 0.114

Asia WGS AF: 0.0300 AC: 104 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Dec 21, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

*803A>G in 3'UTR of SDHD: This variant has been identified in 9.2% of chromosome s from a broad, though clinically and racially unspecified population by the 100 0 Genomes project (dbSNP rs17113461). Although this region can contain elements that regulate mRNA, there is no obvious predicted effect of this variant. *80 3A>G in 3'UTR of SDHD(rs17113461; allele frequency = 9.2%)

Pheochromocytoma Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.6
DANN	Benign	0.76
PhyloP100		-0.071
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17113461; hg19: chr11-111966497;