rs149570245

Positions:

• chr11-112095230-T-A

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.*260T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0157 in 499,770 control chromosomes in the GnomAD database, including 462 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (355 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (107 hom.)
• Consequence: SDHD NM_003002.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.552

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=-0.78).
• BP6: Variant 11-112095230-T-A is Benign according to our data. Variant chr11-112095230-T-A is described in ClinVar as [Benign]. Clinvar id is 165184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDHD	NM_003002.4	c.*260T>A		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.*260T>A		3_prime_UTR_variant	4/4	1	NM_003002.4	ENSP00000364699.3
ENSG00000255292	ENST00000532699.1	n.314+6219T>A		intron_variant		3		ENSP00000456434.1

Frequencies

GnomAD3 genomes AF: 0.0380 AC: 5779 AN: 152186 Hom.: 354 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.0267

GnomAD4 exome AF: 0.00592 AC: 2056 AN: 347466 Hom.: 107 Cov.: 0 AF XY: 0.00483 AC XY: 885 AN XY: 183196

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.00740

Gnomad4 ASJ exome AF: 0.00400

Gnomad4 EAS exome AF: 0.00111

Gnomad4 SAS exome AF: 0.000401

Gnomad4 FIN exome AF: 0.000190

Gnomad4 NFE exome AF: 0.000567

Gnomad4 OTH exome AF: 0.0113

GnomAD4 genome AF: 0.0380 AC: 5791 AN: 152304 Hom.: 355 Cov.: 32 AF XY: 0.0376 AC XY: 2803 AN XY: 74484

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0129

Gnomad4 ASJ AF: 0.00547

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000779

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0334 Hom.: 34

Bravo AF: 0.0436

Asia WGS AF: 0.00722 AC: 25 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 15, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Nov 05, 2013

- -

Pheochromocytoma Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.5
DANN	Benign	0.82

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: rs149570245; hg19: chr11-111965954;