chr5-230978-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1

The NM_004168.4(SDHA):c.873G>A(p.Glu291Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000638 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

SDHA
NM_004168.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.312

Publications

1 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: G2P, Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)
mitochondrial complex II deficiency, nuclear type 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
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: Ambry Genetics, ClinGen
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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 5-230978-G-A is Benign according to our data. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-230978-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 417261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.312 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.0000684 (100/1461618) while in subpopulation SAS AF = 0.00115 (99/86248). AF 95% confidence interval is 0.000964. There are 0 homozygotes in GnomAdExome4. There are 77 alleles in the male GnomAdExome4 subpopulation. Median coverage is 57. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDHA	NM_004168.4 link	c.873G>A	p.Glu291Glu	synonymous_variant	Exon 7 of 15	ENST00000264932.11	NP_004159.2	P31040-1A0A024QZ30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDHA	ENST00000264932.11 link	c.873G>A	p.Glu291Glu	synonymous_variant	Exon 7 of 15	1	NM_004168.4	ENSP00000264932.6		P31040-1
ENSG00000286001	ENST00000651543.1 link	n.873G>A		non_coding_transcript_exon_variant	Exon 7 of 24			ENSP00000499215.1		A0A494C1T6

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000116

AC:

AN:

251038

AF XY:

0.000155

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000684

AC:

100

AN:

1461618

Hom.:

Cov.:

AF XY:

0.000106

AC XY:

AN XY:

727120

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00115

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111826

Other (OTH)

AF:

0.0000166

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000197

AC:

AN:

152352

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41590

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000508

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

May 08, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pheochromocytoma/paraganglioma syndrome 5

Benign:1

Mar 03, 2025

Myriad Genetics, Inc.

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -

Pheochromocytoma/paraganglioma syndrome 5;C5700310:Mitochondrial complex II deficiency, nuclear type 1

Benign:1

Dec 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:1

Aug 21, 2019

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

3.6

(source)

DANN

Benign

0.30

PhyloP100

0.31

Mutation Taster

=99/1

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over