6-159682052-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000636.4(SOD2):c.*441G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 153,582 control chromosomes in the GnomAD database, including 6,118 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 0.28 (6051 hom., cov: 32)
  • Exomes 𝑓: 0.29 (67 hom.)
• Consequence: SOD2 NM_000636.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310

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 (EAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOD2	NM_000636.4	c.*441G>A		3_prime_UTR_variant	5/5	ENST00000538183.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOD2	ENST00000538183.7	c.*441G>A		3_prime_UTR_variant	5/5	1	NM_000636.4	P1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42194 AN: 151914 Hom.: 6049 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.292

GnomAD4 exome AF: 0.285 AC: 442 AN: 1550 Hom.: 67 Cov.: 0 AF XY: 0.308 AC XY: 269 AN XY: 872

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.236

Gnomad4 ASJ exome AF: 0.188

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.329

Gnomad4 FIN exome AF: 0.350

Gnomad4 NFE exome AF: 0.276

Gnomad4 OTH exome AF: 0.297

GnomAD4 genome AF: 0.278 AC: 42219 AN: 152032 Hom.: 6051 Cov.: 32 AF XY: 0.285 AC XY: 21207 AN XY: 74306

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.409

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.291

Alfa AF: 0.286 Hom.: 10811

Bravo AF: 0.268

Asia WGS AF: 0.338 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.5
Dann	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs5746136; hg19: chr6-160103084;