rs11575993

Positions:

• chr6-159688219-G-A

Variant summary

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

The NM_000636.4(SOD2):​c.250C>T​(p.Leu84Phe) variant causes a missense change involving the alteration of a 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SOD2 NM_000636.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.01

Genes affected

SOD2 (HGNC:11180): (superoxide dismutase 2) This gene is a member of the iron/manganese superoxide dismutase family. It encodes a mitochondrial protein that forms a homotetramer and binds one manganese ion per subunit. This protein binds to the superoxide byproducts of oxidative phosphorylation and converts them to hydrogen peroxide and diatomic oxygen. Mutations in this gene have been associated with idiopathic cardiomyopathy (IDC), premature aging, sporadic motor neuron disease, and cancer. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 1. [provided by RefSeq, Apr 2016]

SOD2 (HGNC:):

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
SOD2	NM_000636.4	c.250C>T	p.Leu84Phe	missense_variant	3/5	ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7	c.250C>T	p.Leu84Phe	missense_variant	3/5	1	NM_000636.4	ENSP00000446252.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.25	T;T;.;T;T;T;.
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	.;D;D;D;D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.73	D;D;D;D;D;D;D
MetaSVM	Benign	-0.61	T
MutationAssessor	Pathogenic	3.1	M;M;M;.;.;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.7	D;D;D;D;D;D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0010	D;D;D;D;D;D;D
Sift4G	Uncertain	0.016	D;D;D;.;.;.;D
Polyphen		1.0	D;D;.;.;.;.;.
Vest4		0.73
MutPred		0.55		Gain of catalytic residue at L84 (P = 0.0563);Gain of catalytic residue at L84 (P = 0.0563);Gain of catalytic residue at L84 (P = 0.0563);.;.;.;.;
MVP		0.74
MPC		1.4
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.64
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11575993; hg19: chr6-160109251;