11-112089809-T-C

Position:

• chr11-112089809-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000375549.8(SDHD):​c.314+798T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,054 control chromosomes in the GnomAD database, including 8,214 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (8214 hom., cov: 32)
• Consequence: SDHD ENST00000375549.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDHD	NM_003002.4	c.314+798T>C		intron_variant		ENST00000375549.8	NP_002993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDHD	ENST00000375549.8	c.314+798T>C		intron_variant		1	NM_003002.4	ENSP00000364699	P1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47599 AN: 151936 Hom.: 8213 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.305

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.313 AC: 47609 AN: 152054 Hom.: 8214 Cov.: 32 AF XY: 0.320 AC XY: 23807 AN XY: 74326

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.304

Alfa AF: 0.346 Hom.: 12393

Bravo AF: 0.307

Asia WGS AF: 0.430 AC: 1499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.1
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs10789859; hg19: chr11-111960533;