11-112095583-T-C

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.*613T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.954 in 230,310 control chromosomes in the GnomAD database, including 105,713 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.94 ( 67622 hom., cov: 31)

Exomes 𝑓: 0.99 ( 38091 hom. )

Consequence

SDHD
NM_003002.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.514

Publications

6 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: ClinGen, Orphanet
pheochromocytoma
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
pheochromocytoma/paraganglioma syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
Carney-Stratakis syndrome
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
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: Ambry Genetics, Orphanet
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=-0.91).

BP6

Variant 11-112095583-T-C is Benign according to our data. Variant chr11-112095583-T-C is described in ClinVar as Benign. ClinVar VariationId is 44648.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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
SDHD	NM_003002.4	MANE Select	c.*613T>C	3_prime_UTR	Exon 4 of 4	NP_002993.1
SDHD	NR_077060.2		n.1182T>C	non_coding_transcript_exon	Exon 5 of 5
SDHD	NM_001276506.2		c.*791T>C	3_prime_UTR	Exon 5 of 5	NP_001263435.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SDHD	ENST00000375549.8	TSL:1 MANE Select	c.*613T>C	3_prime_UTR	Exon 4 of 4	ENSP00000364699.3
ENSG00000255292	ENST00000532699.1	TSL:3	n.314+6572T>C	intron	N/A	ENSP00000456434.1
SDHD	ENST00000714087.1		n.*1139T>C	non_coding_transcript_exon	Exon 4 of 4	ENSP00000519378.1

Frequencies

GnomAD3 genomes

AF:

0.938

AC:

142643

AN:

152058

Hom.:

67572

Cov.:

show subpopulations

Gnomad AFR

AF:

0.788

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.970

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.991

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.953

GnomAD4 exome

AF:

0.986

AC:

77051

AN:

78134

Hom.:

38091

Cov.:

AF XY:

0.988

AC XY:

35586

AN XY:

36034

show subpopulations

African (AFR)

AF:

0.782

AC:

2907

AN:

3718

American (AMR)

AF:

0.970

AC:

2412

AN:

2486

Ashkenazi Jewish (ASJ)

AF:

0.999

AC:

4955

AN:

4958

East Asian (EAS)

AF:

1.00

AC:

10782

AN:

10782

South Asian (SAS)

AF:

1.00

AC:

744

AN:

744

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AF:

0.998

AC:

471

AN:

472

European-Non Finnish (NFE)

AF:

0.999

AC:

48370

AN:

48410

Other (OTH)

AF:

0.976

AC:

6352

AN:

6506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

116

155

194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

276

414

552

690

<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:

0.938

AC:

142750

AN:

152176

Hom.:

67622

Cov.:

AF XY:

0.941

AC XY:

69978

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.788

AC:

32697

AN:

41486

American (AMR)

AF:

0.970

AC:

14814

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5180

AN:

5182

South Asian (SAS)

AF:

0.999

AC:

4818

AN:

4822

European-Finnish (FIN)

AF:

1.00

AC:

10595

AN:

10596

Middle Eastern (MID)

AF:

0.990

AC:

291

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

67962

AN:

68032

Other (OTH)

AF:

0.951

AC:

2009

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

379

758

1138

1517

1896

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

904

1808

2712

3616

4520

<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:

0.972

Hom.:

115105

Bravo

AF:

0.929

Asia WGS

AF:

0.982

AC:

3408

AN:

3470

ClinVar

ClinVar submissions as Germline

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

-0.91

CADD

Benign

1.5

(source)

DANN

Benign

0.53

PhyloP100

-0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over