NM_000636.4:c.*3223T>C

Variant names:

• chr6-159679270-A-G
• rs7855
• NM_000636.4:c.*3223T>C

Variant summary

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

The NM_000636.4(SOD2):​c.*3223T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0352 in 152,344 control chromosomes in the GnomAD database, including 114 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 0.035 (114 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SOD2 NM_000636.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.956
• Publications: 34 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0508 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.*3223T>C		3_prime_UTR	Exon 5 of 5	NP_000627.2
	SOD2	NM_001024465.3		c.*48T>C		3_prime_UTR	Exon 6 of 6	NP_001019636.1
	SOD2	NM_001024466.3		c.*48T>C		3_prime_UTR	Exon 5 of 5	NP_001019637.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD2	ENST00000538183.7	TSL:1 MANE Select	c.*3223T>C		3_prime_UTR	Exon 5 of 5	ENSP00000446252.1
	SOD2	ENST00000367055.8	TSL:1	c.*48T>C		3_prime_UTR	Exon 6 of 6	ENSP00000356022.4
	SOD2	ENST00000942970.1		c.*3223T>C		3_prime_UTR	Exon 5 of 5	ENSP00000613029.1

Frequencies

GnomAD3 genomes AF: 0.0352 AC: 5365 AN: 152226 Hom.: 114 Cov.: 33

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0344

Gnomad ASJ AF: 0.0475

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.00930

Gnomad FIN AF: 0.0422

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0522

Gnomad OTH AF: 0.0382

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

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

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0352 AC: 5364 AN: 152344 Hom.: 114 Cov.: 33 AF XY: 0.0333 AC XY: 2482 AN XY: 74504

African (AFR) AF: 0.0110 AC: 459 AN: 41590

American (AMR) AF: 0.0343 AC: 525 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0475 AC: 165 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5194

South Asian (SAS) AF: 0.00931 AC: 45 AN: 4834

European-Finnish (FIN) AF: 0.0422 AC: 448 AN: 10618

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0522 AC: 3553 AN: 68018

Other (OTH) AF: 0.0378 AC: 80 AN: 2114

Alfa AF: 0.0430 Hom.: 152

Bravo AF: 0.0339

Asia WGS AF: 0.00549 AC: 19 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	12
DANN	Benign	0.78
PhyloP100		-0.96
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs7855; hg19: chr6-160100302;