rs770796603

chr1-161314415-C-Achr1-161314415-C-Gchr1-161314415-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003001.5(SDHC):c.10C>A(p.Leu4Met) variant causes a missense 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. 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. L4P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SDHC NM_003001.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247

Genes affected

SDHC (HGNC:10682): (succinate dehydrogenase complex subunit C) This gene encodes one of four nuclear-encoded subunits that comprise succinate dehydrogenase, also known as mitochondrial complex II, a key enzyme complex of the tricarboxylic acid cycle and aerobic respiratory chains of mitochondria. The encoded protein is one of two integral membrane proteins that anchor other subunits of the complex, which form the catalytic core, to the inner mitochondrial membrane. There are several related pseudogenes for this gene on different chromosomes. Mutations in this gene have been associated with paragangliomas. Alternatively spliced transcript variants have been described. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23070428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDHC	NM_003001.5	c.10C>A	p.Leu4Met	missense_variant	1/6	ENST00000367975.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDHC	ENST00000367975.7	c.10C>A	p.Leu4Met	missense_variant	1/6	1	NM_003001.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
Cadd	Benign	16
Dann	Uncertain	0.98
DEOGEN2	Benign	0.15	T;.;.;.;.
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.77	T;T;T;T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.23	T;T;T;T;T
MetaSVM	Uncertain	0.40	D
MutationAssessor	Uncertain	2.2	M;M;M;M;M
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.78	N;N;N;N;N
REVEL	Uncertain	0.42
Sift	Benign	0.037	D;D;D;T;D
Sift4G	Uncertain	0.022	D;D;D;T;D
Polyphen		0.31	B;P;P;P;P
Vest4		0.39
MutPred		0.33		Gain of MoRF binding (P = 0.0795);Gain of MoRF binding (P = 0.0795);Gain of MoRF binding (P = 0.0795);Gain of MoRF binding (P = 0.0795);Gain of MoRF binding (P = 0.0795);
MVP		0.80
MPC		0.39
ClinPred		0.94	D
GERP RS		-0.059
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.63

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: chr1-161284205;