rs5746138

chr6-159681820-T-C

Variant summary

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

The NM_000636.4(SOD2):c.*673A>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 0.0547 in 152,290 control chromosomes in the GnomAD database, including 266 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 0.055 (266 hom., cov: 32)
  • 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: -0.262

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=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOD2	NM_000636.4	c.*673A>G		3_prime_UTR_variant	5/5	ENST00000538183.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOD2	ENST00000538183.7	c.*673A>G		3_prime_UTR_variant	5/5	1	NM_000636.4	P1

Frequencies

GnomAD3 genomes AF: 0.0546 AC: 8314 AN: 152172 Hom.: 266 Cov.: 32

Gnomad AFR AF: 0.0474

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0662

Gnomad ASJ AF: 0.0738

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.0701

Gnomad FIN AF: 0.0417

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0592

Gnomad OTH AF: 0.0598

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0547 AC: 8323 AN: 152290 Hom.: 266 Cov.: 32 AF XY: 0.0548 AC XY: 4082 AN XY: 74468

Gnomad4 AFR AF: 0.0475

Gnomad4 AMR AF: 0.0661

Gnomad4 ASJ AF: 0.0738

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.0704

Gnomad4 FIN AF: 0.0417

Gnomad4 NFE AF: 0.0592

Gnomad4 OTH AF: 0.0592

Alfa AF: 0.0495 Hom.: 24

Bravo AF: 0.0542

Asia WGS AF: 0.0310 AC: 111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	3.4
Dann	Benign	0.87

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: rs5746138; hg19: chr6-160102852;