rs2855262

chr4-24800354-T-Cchr4-24800354-T-G

Variant summary

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

The NM_003102.4(SOD3):c.*110T>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 0.61 in 1,150,044 control chromosomes in the GnomAD database, including 222,949 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 0.50 (22328 hom., cov: 30)
  • Exomes 𝑓: 0.63 (200621 hom.)
• Consequence: SOD3 NM_003102.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.555

Genes affected

SOD3 (HGNC:11181): (superoxide dismutase 3) This gene encodes a member of the superoxide dismutase (SOD) protein family. SODs are antioxidant enzymes that catalyze the conversion of superoxide radicals into hydrogen peroxide and oxygen, which may protect the brain, lungs, and other tissues from oxidative stress. Proteolytic processing of the encoded protein results in the formation of two distinct homotetramers that differ in their ability to interact with the extracellular matrix (ECM). Homotetramers consisting of the intact protein, or type C subunit, exhibit high affinity for heparin and are anchored to the ECM. Homotetramers consisting of a proteolytically cleaved form of the protein, or type A subunit, exhibit low affinity for heparin and do not interact with the ECM. A mutation in this gene may be associated with increased heart disease risk. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOD3	NM_003102.4	c.*110T>C		3_prime_UTR_variant	2/2	ENST00000382120.4
SOD3	XR_427488.2	n.928T>C		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOD3	ENST00000382120.4	c.*110T>C		3_prime_UTR_variant	2/2	1	NM_003102.4	P1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75769 AN: 151636 Hom.: 22331 Cov.: 30

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.531

GnomAD4 exome AF: 0.627 AC: 626093 AN: 998290 Hom.: 200621 Cov.: 14 AF XY: 0.627 AC XY: 301452 AN XY: 480780

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.515

Gnomad4 ASJ exome AF: 0.619

Gnomad4 EAS exome AF: 0.340

Gnomad4 SAS exome AF: 0.528

Gnomad4 FIN exome AF: 0.686

Gnomad4 NFE exome AF: 0.651

Gnomad4 OTH exome AF: 0.596

GnomAD4 genome AF: 0.499 AC: 75768 AN: 151754 Hom.: 22328 Cov.: 30 AF XY: 0.502 AC XY: 37202 AN XY: 74128

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.651

Gnomad4 OTH AF: 0.529

Alfa AF: 0.590 Hom.: 16526

Bravo AF: 0.473

Asia WGS AF: 0.439 AC: 1529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.5
Dann	Benign	0.65

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: rs2855262; hg19: chr4-24801976; COSMIC: COSV66125735; COSMIC: COSV66125735;