5-228163-CTT-CT

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_004168.4(SDHA):c.622-13delT 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:7

Conservation

PhyloP100: -0.708

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

hereditary pheochromocytoma-paraganglioma
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
pheochromocytoma/paraganglioma syndrome 5
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Illumina, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
mitochondrial complex II deficiency, nuclear type 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
neurodegeneration with ataxia and late-onset optic atrophy
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
Leigh syndrome
Inheritance: AR Classification: MODERATE Submitted by: ClinGen, Ambry Genetics
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
gastrointestinal stromal tumor
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Leigh syndrome with leukodystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
mitochondrial complex II deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
dilated cardiomyopathy 1GG
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

SDHA links:

ENSG00000286001 (HGNC:):

ENSG00000286001 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 259247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004168.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SDHA	NM_004168.4	MANE Select	c.622-13delT	intron	N/A	NP_004159.2	P31040-1
SDHA	NM_001294332.2		c.478-13delT	intron	N/A	NP_001281261.1	P31040-2
SDHA	NM_001330758.2		c.622-13delT	intron	N/A	NP_001317687.1	D6RFM5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SDHA	ENST00000264932.11	TSL:1 MANE Select	c.622-13delT	intron	N/A	ENSP00000264932.6	P31040-1
ENSG00000286001	ENST00000651543.1		n.622-13delT	intron	N/A	ENSP00000499215.1	A0A494C1T6
SDHA	ENST00000874235.1		c.622-13delT	intron	N/A	ENSP00000544294.1

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

GnomAD2 exomes

AF:

0.143

AC:

34531

AN:

240708

AF XY:

0.136

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 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

African (AFR)

AF:

0.540

AC:

17911

AN:

33158

American (AMR)

AF:

0.188

AC:

8377

AN:

44484

Ashkenazi Jewish (ASJ)

AF:

0.166

AC:

4294

AN:

25924

East Asian (EAS)

AF:

0.0486

AC:

1904

AN:

39182

South Asian (SAS)

AF:

0.0903

AC:

7753

AN:

85858

European-Finnish (FIN)

AF:

0.0893

AC:

4676

AN:

52376

Middle Eastern (MID)

AF:

0.141

AC:

788

AN:

5574

European-Non Finnish (NFE)

AF:

0.131

AC:

144042

AN:

1100184

Other (OTH)

AF:

0.156

AC:

9349

AN:

59752

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

7621

15242

22862

30483

38104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5410

10820

16230

21640

27050

<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:

0.241

AC:

36399

AN:

151248

Hom.:

6828

Cov.:

AF XY:

0.235

AC XY:

17358

AN XY:

73882

show subpopulations

African (AFR)

AF:

0.525

AC:

21622

AN:

41154

American (AMR)

AF:

0.221

AC:

3354

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.166

AC:

574

AN:

3458

East Asian (EAS)

AF:

0.0554

AC:

285

AN:

5144

South Asian (SAS)

AF:

0.0893

AC:

426

AN:

4772

European-Finnish (FIN)

AF:

0.0820

AC:

856

AN:

10444

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.125

AC:

8461

AN:

67782

Other (OTH)

AF:

0.231

AC:

480

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

1129

2258

3386

4515

5644

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<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:

0.0774

Hom.:

100

Bravo

AF:

0.267

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Hereditary cancer-predisposing syndrome (1)

Pheochromocytoma/paraganglioma syndrome 5 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.71

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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