chr6-159692858-C-A

Variant names:

• chr6-159692858-C-A
• rs5746096
• NM_000636.4:c.29G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000636.4(SOD2):​c.29G>T​(p.Ser10Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000657 in 1,605,776 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00055 (1 hom.)
• Consequence: SOD2 NM_000636.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75
• Publications: 8 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005635321).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2	NM_000636.4	c.29G>T	p.Ser10Ile	missense_variant	Exon 2 of 5	ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7	c.29G>T	p.Ser10Ile	missense_variant	Exon 2 of 5	1	NM_000636.4	ENSP00000446252.1

Frequencies

GnomAD3 genomes AF: 0.00164 AC: 250 AN: 152218 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00318

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000949 AC: 219 AN: 230756 AF XY: 0.000894

Gnomad AFR exome AF: 0.00310

Gnomad AMR exome AF: 0.00197

Gnomad ASJ exome AF: 0.00241

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000439

Gnomad OTH exome AF: 0.00244

GnomAD4 exome AF: 0.000554 AC: 805 AN: 1453440 Hom.: 1 Cov.: 32 AF XY: 0.000556 AC XY: 402 AN XY: 722686

African (AFR) AF: 0.00372 AC: 124 AN: 33332

American (AMR) AF: 0.00234 AC: 102 AN: 43540

Ashkenazi Jewish (ASJ) AF: 0.00306 AC: 79 AN: 25858

East Asian (EAS) AF: 0.00 AC: 0 AN: 39488

South Asian (SAS) AF: 0.000971 AC: 83 AN: 85442

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51164

Middle Eastern (MID) AF: 0.00355 AC: 20 AN: 5634

European-Non Finnish (NFE) AF: 0.000270 AC: 299 AN: 1108880

Other (OTH) AF: 0.00163 AC: 98 AN: 60102

GnomAD4 genome AF: 0.00164 AC: 250 AN: 152336 Hom.: 0 Cov.: 31 AF XY: 0.00176 AC XY: 131 AN XY: 74504

African (AFR) AF: 0.00317 AC: 132 AN: 41576

American (AMR) AF: 0.00483 AC: 74 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00518 AC: 18 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68032

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00103 Hom.: 15

Bravo AF: 0.00219

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000800 AC: 97

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T;T;.;.;.;T;T;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.74	.;T;.;T;T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.0056	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L;L;L;L;.;.;.
PhyloP100		1.7
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.2	N;N;N;N;N;N;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.029	D;D;D;T;D;D;D;D
Sift4G	Uncertain	0.059	T;T;T;T;T;.;.;D
Polyphen		0.072	B;B;.;.;.;.;.;D
Vest4		0.30
MVP		0.54
MPC		0.56
ClinPred		0.026	T
GERP RS		3.0
PromoterAI		0.0058	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.51
Mutation Taster		=91/9	polymorphism

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: rs5746096; hg19: chr6-160113890;