Variant 5-228163-CTT-CT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_004168.4(SDHA):c.622-13del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,597,740 control chromosomes in the GnomAD database, including 23,812 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 6828 hom., cov: 26)

Exomes 𝑓: 0.14 ( 16984 hom. )

Consequence

SDHA
NM_004168.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.708

Variant links:

Genes affected

SDHA (HGNC:10680): (succinate dehydrogenase complex flavoprotein subunit A) This gene encodes a major catalytic subunit of succinate-ubiquinone oxidoreductase, a complex of the mitochondrial respiratory chain. The complex is composed of four nuclear-encoded subunits and is localized in the mitochondrial inner membrane. Mutations in this gene have been associated with a form of mitochondrial respiratory chain deficiency known as Leigh Syndrome. A pseudogene has been identified on chromosome 3q29. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

SDHA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 5-228163-CT-C is Benign according to our data. Variant chr5-228163-CT-C is described in ClinVar as [Benign]. Clinvar id is 259247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-228163-CT-C is described in Lovd as [Benign]. Variant chr5-228163-CT-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDHA	NM_004168.4 linkuse as main transcript	c.622-13del		intron_variant		ENST00000264932.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDHA	ENST00000264932.11 linkuse as main transcript	c.622-13del		intron_variant		1	NM_004168.4	P1	P31040-1

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

36327

AN:

151134

Hom.:

6801

Cov.:

show subpopulations

Gnomad AFR

AF:

0.525

Gnomad AMI

AF:

0.307

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.166

Gnomad EAS

AF:

0.0559

Gnomad SAS

AF:

0.0890

Gnomad FIN

AF:

0.0820

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.234

GnomAD3 exomes

AF:

0.143

AC:

34531

AN:

240708

Hom.:

3142

AF XY:

0.136

AC XY:

17776

AN XY:

130746

show subpopulations

Gnomad AFR exome

AF:

0.510

Gnomad AMR exome

AF:

0.179

Gnomad ASJ exome

AF:

0.149

Gnomad EAS exome

AF:

0.0590

Gnomad SAS exome

AF:

0.0871

Gnomad FIN exome

AF:

0.0869

Gnomad NFE exome

AF:

0.122

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.138

AC:

199094

AN:

1446492

Hom.:

16984

Cov.:

AF XY:

0.135

AC XY:

97176

AN XY:

719932

show subpopulations

Gnomad4 AFR exome

AF:

0.540

Gnomad4 AMR exome

AF:

0.188

Gnomad4 ASJ exome

AF:

0.166

Gnomad4 EAS exome

AF:

0.0486

Gnomad4 SAS exome

AF:

0.0903

Gnomad4 FIN exome

AF:

0.0893

Gnomad4 NFE exome

AF:

0.131

Gnomad4 OTH exome

AF:

0.156

GnomAD4 genome

AF:

0.241

AC:

36399

AN:

151248

Hom.:

6828

Cov.:

AF XY:

0.235

AC XY:

17358

AN XY:

73882

show subpopulations

Gnomad4 AFR

AF:

0.525

Gnomad4 AMR

AF:

0.221

Gnomad4 ASJ

AF:

0.166

Gnomad4 EAS

AF:

0.0554

Gnomad4 SAS

AF:

0.0893

Gnomad4 FIN

AF:

0.0820

Gnomad4 NFE

AF:

0.125

Gnomad4 OTH

AF:

0.231

Alfa

AF:

0.0774

Hom.:

100

Bravo

AF:

0.267

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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