NM_000636.4:c.*4265A>G

Variant names:

• chr6-159678228-T-C
• rs6917589
• NM_000636.4:c.*4265A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000636.4(SOD2):​c.*4265A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,090 control chromosomes in the GnomAD database, including 4,012 homozygotes. 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: 𝑓 0.22 (4008 hom., cov: 32)
  • Exomes 𝑓: 0.26 (4 hom.)
• Consequence: SOD2 NM_000636.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555
• Publications: 22 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000636.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD2	NM_000636.4	MANE Select	c.*4265A>G		3_prime_UTR	Exon 5 of 5	NP_000627.2
	SOD2	NM_001322814.2		c.*4265A>G		3_prime_UTR	Exon 4 of 4	NP_001309743.1
	SOD2	NM_001322819.2		c.*4265A>G		3_prime_UTR	Exon 5 of 5	NP_001309748.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD2	ENST00000538183.7	TSL:1 MANE Select	c.*4265A>G		3_prime_UTR	Exon 5 of 5	ENSP00000446252.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33816 AN: 151892 Hom.: 4004 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.263 AC: 21 AN: 80 Hom.: 4 Cov.: 0 AF XY: 0.288 AC XY: 19 AN XY: 66

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.288 AC: 19 AN: 66

Other (OTH) AF: 0.00 AC: 0 AN: 8

GnomAD4 genome AF: 0.223 AC: 33834 AN: 152010 Hom.: 4008 Cov.: 32 AF XY: 0.230 AC XY: 17068 AN XY: 74270

African (AFR) AF: 0.151 AC: 6253 AN: 41502

American (AMR) AF: 0.237 AC: 3617 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 696 AN: 3470

East Asian (EAS) AF: 0.402 AC: 2067 AN: 5146

South Asian (SAS) AF: 0.272 AC: 1308 AN: 4810

European-Finnish (FIN) AF: 0.328 AC: 3466 AN: 10562

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15849 AN: 67952

Other (OTH) AF: 0.229 AC: 485 AN: 2114

Alfa AF: 0.231 Hom.: 6635

Bravo AF: 0.214

Asia WGS AF: 0.304 AC: 1056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.77
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6917589; hg19: chr6-160099260;