rs1141718

Variant names:

• chr6-159688224-A-G
• rs1141718
• NM_000636.4:c.245T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-159688224-A-G
• chr6-159688224-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000636.4(SOD2):​c.245T>C​(p.Ile82Thr) variant causes a missense change involving the alteration of a 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SOD2 NM_000636.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.21
• Publications: 15 publications found

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 Gene-Disease associations (from GenCC):

• cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28869992).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2	NM_000636.4	c.245T>C	p.Ile82Thr	missense_variant	Exon 3 of 5	ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7	c.245T>C	p.Ile82Thr	missense_variant	Exon 3 of 5	1	NM_000636.4	ENSP00000446252.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T;T;.;T;T;T;.
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.058
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.79	.;T;T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.29	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M;M;M;.;.;.;.
PhyloP100		9.2
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-4.3	D;D;D;D;D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.012	D;D;T;D;D;D;D
Sift4G	Uncertain	0.025	D;D;D;.;.;.;D
Polyphen		0.0010	B;B;.;.;.;.;.
Vest4		0.29
MutPred		0.45		Gain of disorder (P = 0.0424);Gain of disorder (P = 0.0424);Gain of disorder (P = 0.0424);.;.;.;.;
MVP		0.58
MPC		0.65
ClinPred		0.95	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.46
gMVP		0.64
Mutation Taster		=47/53	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1141718; hg19: chr6-160109256;