rs17113461

Variant names:

Variant summary

Our verdict is Benign. The variant received -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:3

Conservation

PhyloP100: -0.0710

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

hereditary pheochromocytoma-paraganglioma
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
pheochromocytoma
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
pheochromocytoma/paraganglioma syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
Carney-Stratakis syndrome
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
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: Orphanet, Ambry Genetics
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

SDHD links:

ENSG00000255292 (HGNC:):

ENSG00000255292 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SDHD	NM_003002.4	MANE Select	c.*803A>G	3_prime_UTR	Exon 4 of 4	NP_002993.1	O14521-1
SDHD	NM_001276506.2		c.*981A>G	3_prime_UTR	Exon 5 of 5	NP_001263435.1	O14521-4
SDHD	NM_001276504.2		c.*803A>G	3_prime_UTR	Exon 3 of 3	NP_001263433.1	O14521-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SDHD	ENST00000375549.8	TSL:1 MANE Select	c.*803A>G	3_prime_UTR	Exon 4 of 4	ENSP00000364699.3	O14521-1
ENSG00000255292	ENST00000532699.1	TSL:3	n.314+6762A>G	intron	N/A	ENSP00000456434.1	H3BRW5
SDHD	ENST00000938877.1		c.*803A>G	3_prime_UTR	Exon 4 of 4	ENSP00000608936.1

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

African (AFR)

AF:

0.271

AC:

624

AN:

2306

American (AMR)

AF:

0.0442

AC:

AN:

1516

Ashkenazi Jewish (ASJ)

AF:

0.0102

AC:

AN:

3526

East Asian (EAS)

AF:

0.000398

AC:

AN:

7536

South Asian (SAS)

AF:

0.00433

AC:

AN:

462

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.0311

AC:

AN:

322

European-Non Finnish (NFE)

AF:

0.0107

AC:

354

AN:

33210

Other (OTH)

AF:

0.0425

AC:

189

AN:

4444

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

140

186

233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0996

AC:

15168

AN:

152226

Hom.:

2219

Cov.:

AF XY:

0.0969

AC XY:

7215

AN XY:

74452

show subpopulations

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:

AN:

3470

East Asian (EAS)

AF:

0.00308

AC:

AN:

5194

South Asian (SAS)

AF:

0.00455

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00490

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0116

AC:

791

AN:

68020

Other (OTH)

AF:

0.0757

AC:

160

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

560

1121

1681

2242

2802

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0492

Hom.:

998

Bravo

AF:

0.114

Asia WGS

AF:

0.0300

AC:

104

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Pheochromocytoma (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

6.6

(source)

DANN

Benign

0.76

PhyloP100

-0.071

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over