rs9919624

chr11-112088838-A-G

Variant summary

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

The NM_003002.4(SDHD):c.170-29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0275 in 1,611,516 control chromosomes in the GnomAD database, including 5,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 2532 hom., cov: 32)

Exomes 𝑓: 0.019 ( 2508 hom. )

Consequence

SDHD
NM_003002.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.22

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 11-112088838-A-G is Benign according to our data. Variant chr11-112088838-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 440261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-112088838-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 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.170-29A>G		intron_variant		ENST00000375549.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDHD	ENST00000375549.8 linkuse as main transcript	c.170-29A>G		intron_variant		1	NM_003002.4	P1	O14521-1

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16101

AN:

152114

Hom.:

2501

Cov.:

show subpopulations

Gnomad AFR

AF:

0.343

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0497

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.00490

Gnomad MID

AF:

0.0541

Gnomad NFE

AF:

0.0118

Gnomad OTH

AF:

0.0817

GnomAD3 exomes

AF:

0.0341

AC:

8552

AN:

251018

Hom.:

1048

AF XY:

0.0272

AC XY:

3687

AN XY:

135666

show subpopulations

Gnomad AFR exome

AF:

0.358

Gnomad AMR exome

AF:

0.0247

Gnomad ASJ exome

AF:

0.0156

Gnomad EAS exome

AF:

0.00190

Gnomad SAS exome

AF:

0.00369

Gnomad FIN exome

AF:

0.00471

Gnomad NFE exome

AF:

0.0119

Gnomad OTH exome

AF:

0.0227

GnomAD4 exome

AF:

0.0193

AC:

28183

AN:

1459284

Hom.:

2508

Cov.:

AF XY:

0.0179

AC XY:

12978

AN XY:

726000

show subpopulations

Gnomad4 AFR exome

AF:

0.365

Gnomad4 AMR exome

AF:

0.0284

Gnomad4 ASJ exome

AF:

0.0144

Gnomad4 EAS exome

AF:

0.00111

Gnomad4 SAS exome

AF:

0.00392

Gnomad4 FIN exome

AF:

0.00451

Gnomad4 NFE exome

AF:

0.0104

Gnomad4 OTH exome

AF:

0.0338

GnomAD4 genome

AF:

0.106

AC:

16174

AN:

152232

Hom.:

2532

Cov.:

AF XY:

0.103

AC XY:

7687

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.344

Gnomad4 AMR

AF:

0.0496

Gnomad4 ASJ

AF:

0.0187

Gnomad4 EAS

AF:

0.00309

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.00490

Gnomad4 NFE

AF:

0.0118

Gnomad4 OTH

AF:

0.0809

Alfa

AF:

0.0367

Hom.:

301

Bravo

AF:

0.121

Asia WGS

AF:

0.0310

AC:

107

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Mar 10, 2020	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Aug 15, 2023

- -

Pheochromocytoma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Paragangliomas 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Mitochondrial complex 2 deficiency, nuclear type 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Paragangliomas 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

Cadd

Benign

3.8

Dann

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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