6-159679270-A-G

Position:

• chr6-159679270-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOD2	NM_000636.4	c.*3223T>C		3_prime_UTR_variant	5/5	ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7	c.*3223T>C		3_prime_UTR_variant	5/5	1	NM_000636.4	ENSP00000446252	P1

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

Gnomad4 NFE exome AF: 0.00

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

Gnomad4 AFR AF: 0.0110

Gnomad4 AMR AF: 0.0343

Gnomad4 ASJ AF: 0.0475

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.00931

Gnomad4 FIN AF: 0.0422

Gnomad4 NFE AF: 0.0522

Gnomad4 OTH AF: 0.0378

Alfa AF: 0.0467 Hom.: 107

Bravo AF: 0.0339

Asia WGS AF: 0.00549 AC: 19 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	12
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs7855; hg19: chr6-160100302;