Variant 11-112095773-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0710

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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	UniProt
SDHD	NM_003002.4 linkuse as main transcript	c.*803A>G		3_prime_UTR_variant	4/4	ENST00000375549.8

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDHD	ENST00000375549.8 linkuse as main transcript	c.*803A>G	3_prime_UTR_variant	4/4	1	NM_003002.4	P1	O14521-1
SDHD	ENST00000528021.6 linkuse as main transcript	c.314+6762A>G	intron_variant		3
SDHD	ENST00000534010.2 linkuse as main transcript	c.314+6762A>G	intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0992

AC:

15096

AN:

152108

Hom.:

2190

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0232

AC XY:

576

AN XY:

24838

show subpopulations

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.:

AF XY:

0.0969

AC XY:

7215

AN XY:

74452

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over