4-24800327-C-T

Position:

• chr4-24800327-C-T

Variant summary

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

The NM_003102.4(SOD3):​c.*83C>T 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 1,270,026 control chromosomes in the GnomAD database, including 245,928 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 0.49 (22098 hom., cov: 30)
  • Exomes 𝑓: 0.63 (223830 hom.)
• Consequence: SOD3 NM_003102.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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]

SOD3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOD3	NM_003102.4	c.*83C>T		3_prime_UTR_variant	2/2	ENST00000382120.4	NP_003093.2
SOD3	XR_427488.2	n.901C>T		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOD3	ENST00000382120.4	c.*83C>T		3_prime_UTR_variant	2/2	1	NM_003102.4	ENSP00000371554.3

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74785 AN: 151670 Hom.: 22101 Cov.: 30

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.526

GnomAD4 exome AF: 0.625 AC: 699306 AN: 1118240 Hom.: 223830 Cov.: 18 AF XY: 0.625 AC XY: 336596 AN XY: 538768

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.510

Gnomad4 ASJ exome AF: 0.615

Gnomad4 EAS exome AF: 0.339

Gnomad4 SAS exome AF: 0.525

Gnomad4 FIN exome AF: 0.689

Gnomad4 NFE exome AF: 0.650

Gnomad4 OTH exome AF: 0.594

GnomAD4 genome AF: 0.493 AC: 74782 AN: 151786 Hom.: 22098 Cov.: 30 AF XY: 0.496 AC XY: 36750 AN XY: 74164

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.707

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.524

Alfa AF: 0.584 Hom.: 16848

Bravo AF: 0.466

Asia WGS AF: 0.434 AC: 1509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
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: rs2695232; hg19: chr4-24801949; COSMIC: COSV66125733; COSMIC: COSV66125733;