Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The ENST00000264932.11(SDHA):c.24G>A(p.Ser8Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S8S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SDHA
ENST00000264932.11 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0870

Publications

0 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 links:

ENSG00000286001 (HGNC:):

ENSG00000286001 links:

CCDC127 (HGNC:30520): (coiled-coil domain containing 127) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CCDC127 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 5-218379-G-A is Benign according to our data. Variant chr5-218379-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1792225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.087 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000264932.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SDHA	NM_004168.4	MANE Select	c.24G>A	p.Ser8Ser	synonymous	Exon 1 of 15	NP_004159.2
SDHA	NM_001294332.2		c.24G>A	p.Ser8Ser	synonymous	Exon 1 of 14	NP_001281261.1
SDHA	NM_001330758.2		c.24G>A	p.Ser8Ser	synonymous	Exon 1 of 13	NP_001317687.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SDHA	ENST00000264932.11	TSL:1 MANE Select	c.24G>A	p.Ser8Ser	synonymous	Exon 1 of 15	ENSP00000264932.6
ENSG00000286001	ENST00000651543.1		n.24G>A		non_coding_transcript_exon	Exon 1 of 24	ENSP00000499215.1
SDHA	ENST00000510361.5	TSL:2	c.24G>A	p.Ser8Ser	synonymous	Exon 1 of 14	ENSP00000427703.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1303048

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

643350

African (AFR)

AF:

0.00

AC:

AN:

26824

American (AMR)

AF:

0.00

AC:

AN:

24968

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20234

East Asian (EAS)

AF:

0.00

AC:

AN:

31008

South Asian (SAS)

AF:

0.00

AC:

AN:

65052

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33700

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3668

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1044294

Other (OTH)

AF:

0.00

AC:

AN:

53300

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary cancer-predisposing syndrome (1)

Pheochromocytoma/paraganglioma syndrome 5 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

6.6

(source)

DANN

Benign

0.90

PhyloP100

-0.087

PromoterAI

-0.042

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Mutation Taster

=100/0

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

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

rs1060505007

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over