rs878854635

Positions:

• chr5-228257-C-A
• chr5-228257-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000264932.11(SDHA):​c.694C>A​(p.Arg232Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R232C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SDHA ENST00000264932.11 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.778

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDHA	NM_004168.4	c.694C>A	p.Arg232Ser	missense_variant	6/15	ENST00000264932.11	NP_004159.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDHA	ENST00000264932.11	c.694C>A	p.Arg232Ser	missense_variant	6/15	1	NM_004168.4	ENSP00000264932	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;.;.
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.70	D
LIST_S2	Pathogenic	0.97	D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.60	D;D;D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	1.4	L;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.086	T;T;T
Sift4G	Benign	0.85	T;T;T
Polyphen		0.79	P;D;.
Vest4		0.55
MutPred		0.46		Gain of glycosylation at R232 (P = 0.0173);Gain of glycosylation at R232 (P = 0.0173);.;
MVP		0.66
MPC		1.3
ClinPred		0.60	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.38
gMVP		0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-228372;