Variant 1-161362321-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_003001.5(SDHC):c.406-8G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0078 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0049 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SDHC
NM_003001.5 splice_region, intron

Scores

Splicing: ADA: 0.00001562

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: -0.0700

Variant links:

Genes affected

SDHC (HGNC:10682): (succinate dehydrogenase complex subunit C) This gene encodes one of four nuclear-encoded subunits that comprise succinate dehydrogenase, also known as mitochondrial complex II, a key enzyme complex of the tricarboxylic acid cycle and aerobic respiratory chains of mitochondria. The encoded protein is one of two integral membrane proteins that anchor other subunits of the complex, which form the catalytic core, to the inner mitochondrial membrane. There are several related pseudogenes for this gene on different chromosomes. Mutations in this gene have been associated with paragangliomas. Alternatively spliced transcript variants have been described. [provided by RefSeq, May 2013]

SDHC links:

SDHC (HGNC:):

SDHC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 1-161362321-G-T is Benign according to our data. Variant chr1-161362321-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 414250.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1, Benign=1}. Variant chr1-161362321-G-T is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDHC	NM_003001.5 linkuse as main transcript	c.406-8G>T		splice_region_variant, intron_variant		ENST00000367975.7	NP_002992.1	Q99643-1A0A0S2Z4B7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDHC	ENST00000367975.7 linkuse as main transcript	c.406-8G>T		splice_region_variant, intron_variant		1	NM_003001.5	ENSP00000356953.3		Q99643-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

650

AN:

83732

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00851

Gnomad AMI

AF:

0.00568

Gnomad AMR

AF:

0.00742

Gnomad ASJ

AF:

0.00265

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.00360

Gnomad FIN

AF:

0.0270

Gnomad MID

AF:

0.00735

Gnomad NFE

AF:

0.00610

Gnomad OTH

AF:

0.00935

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00492

AC:

5898

AN:

1197992

Hom.:

Cov.:

AF XY:

0.00506

AC XY:

3023

AN XY:

597514

show subpopulations

Gnomad4 AFR exome

AF:

0.0115

Gnomad4 AMR exome

AF:

0.0226

Gnomad4 ASJ exome

AF:

0.00699

Gnomad4 EAS exome

AF:

0.00699

Gnomad4 SAS exome

AF:

0.0100

Gnomad4 FIN exome

AF:

0.0382

Gnomad4 NFE exome

AF:

0.00205

Gnomad4 OTH exome

AF:

0.00470

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00778

AC:

652

AN:

83788

Hom.:

Cov.:

AF XY:

0.00779

AC XY:

312

AN XY:

40068

show subpopulations

Gnomad4 AFR

AF:

0.00848

Gnomad4 AMR

AF:

0.00754

Gnomad4 ASJ

AF:

0.00265

Gnomad4 EAS

AF:

0.00305

Gnomad4 SAS

AF:

0.00361

Gnomad4 FIN

AF:

0.0270

Gnomad4 NFE

AF:

0.00610

Gnomad4 OTH

AF:

0.00924

Alfa

AF:

0.0496

Hom.:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Hereditary cancer-predisposing syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2016

The c.406-8G>T intronic alteration consists of a G to T substitution 8 nucleotides before coding exon 6 in the SDHC gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Dec 19, 2018

- -

Gastrointestinal stromal tumor;C1854336:Paragangliomas 3

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 11, 2023

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hereditary pheochromocytoma-paraganglioma

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

All of Us Research Program, National Institutes of Health

May 14, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.72

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000016

dbscSNV1_RF

Benign

0.0

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