rs5746129

chr6-159684911-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000636.4(SOD2):c.466C>T(p.Arg156Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,146 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R156Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: SOD2 NM_000636.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.37

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16848639).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOD2	NM_000636.4	c.466C>T	p.Arg156Trp	missense_variant	4/5	ENST00000538183.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOD2	ENST00000538183.7	c.466C>T	p.Arg156Trp	missense_variant	4/5	1	NM_000636.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251090 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135730

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461146 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 726914

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000208 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.42
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.33	T;T;.;.;T;T;T;.
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.60	D
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.17	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.23	N;N;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;N;N;N;N;N
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.8	D;D;D;D;D;N;D;D
REVEL	Benign	0.061
Sift	Uncertain	0.016	D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.010	D;D;D;D;.;.;.;D
Polyphen		0.0	B;B;.;.;.;.;.;.
Vest4		0.18
MutPred		0.31		Gain of methylation at K154 (P = 0.1087);Gain of methylation at K154 (P = 0.1087);.;.;.;.;.;.;
MVP		0.59
MPC		0.53
ClinPred		0.56	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs5746129; hg19: chr6-160105943;