4-24800327-C-T

Variant names:

• chr4-24800327-C-T
• rs2695232
• NM_003102.4:c.*83C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SOD3	NM_003102.4	c.*83C>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000382120.4	NP_003093.2
SOD3	XR_427488.2	n.901C>T		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD3	ENST00000382120.4	c.*83C>T		3_prime_UTR_variant	Exon 2 of 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

African (AFR) AF: 0.131 AC: 2866 AN: 21954

American (AMR) AF: 0.510 AC: 4200 AN: 8234

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 9150 AN: 14890

East Asian (EAS) AF: 0.339 AC: 8725 AN: 25738

South Asian (SAS) AF: 0.525 AC: 20264 AN: 38630

European-Finnish (FIN) AF: 0.689 AC: 28314 AN: 41072

Middle Eastern (MID) AF: 0.551 AC: 1664 AN: 3018

European-Non Finnish (NFE) AF: 0.650 AC: 597295 AN: 919558

Other (OTH) AF: 0.594 AC: 26828 AN: 45146

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

African (AFR) AF: 0.159 AC: 6600 AN: 41448

American (AMR) AF: 0.537 AC: 8202 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2108 AN: 3470

East Asian (EAS) AF: 0.368 AC: 1869 AN: 5078

South Asian (SAS) AF: 0.510 AC: 2446 AN: 4800

European-Finnish (FIN) AF: 0.707 AC: 7467 AN: 10558

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.650 AC: 44118 AN: 67848

Other (OTH) AF: 0.524 AC: 1106 AN: 2110

Alfa AF: 0.554 Hom.: 27882

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
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2695232; hg19: chr4-24801949; COSMIC: COSV66125733; COSMIC: COSV66125733;