rs17113461

Positions:

• chr11-112095773-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000255292 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDHD	NM_003002.4	c.*803A>G		3_prime_UTR_variant	4/4	ENST00000375549.8	NP_002993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDHD	ENST00000375549.8	c.*803A>G		3_prime_UTR_variant	4/4	1	NM_003002.4	ENSP00000364699.3
ENSG00000255292	ENST00000532699.1	n.314+6762A>G		intron_variant		3		ENSP00000456434.1

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

Gnomad4 AFR exome AF: 0.271

Gnomad4 AMR exome AF: 0.0442

Gnomad4 ASJ exome AF: 0.0102

Gnomad4 EAS exome AF: 0.000398

Gnomad4 SAS exome AF: 0.00433

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0107

Gnomad4 OTH exome AF: 0.0425

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

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.0456

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.00308

Gnomad4 SAS AF: 0.00455

Gnomad4 FIN AF: 0.00490

Gnomad4 NFE AF: 0.0116

Gnomad4 OTH AF: 0.0757

Alfa AF: 0.0305 Hom.: 356

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

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Dec 21, 2012

*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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.6
DANN	Benign	0.76

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

LitVar

Other links and lift over

dbSNP: rs17113461; hg19: chr11-111966497;