Genetic Variant SOD3:c.*546T>C (chr4-24800790-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003102.4(SOD3):c.*546T>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 0.0904 in 157,366 control chromosomes in the GnomAD database, including 1,223 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 0.092 ( 1215 hom., cov: 32)

Exomes 𝑓: 0.037 ( 8 hom. )

Consequence

SOD3
NM_003102.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.591

Publications

9 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD3	NM_003102.4 link	c.*546T>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000382120.4	NP_003093.2
SOD3	XR_427488.2 link	n.1274T>C		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD3	ENST00000382120.4 link	c.*546T>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_003102.4	ENSP00000371554.3

Frequencies

GnomAD3 genomes

AF:

0.0921

AC:

13998

AN:

152020

Hom.:

1205

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.0828

Gnomad EAS

AF:

0.0478

Gnomad SAS

AF:

0.0255

Gnomad FIN

AF:

0.0346

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0260

Gnomad OTH

AF:

0.0817

GnomAD4 exome

AF:

0.0373

AC:

195

AN:

5228

Hom.:

Cov.:

AF XY:

0.0455

AC XY:

127

AN XY:

2790

show subpopulations

African (AFR)

AF:

0.150

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.0625

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0374

AC:

180

AN:

4808

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0265

AC:

AN:

302

Other (OTH)

AF:

0.0517

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0923

AC:

14038

AN:

152138

Hom.:

1215

Cov.:

AF XY:

0.0934

AC XY:

6943

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.219

AC:

9073

AN:

41492

American (AMR)

AF:

0.129

AC:

1978

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0828

AC:

287

AN:

3468

East Asian (EAS)

AF:

0.0479

AC:

248

AN:

5174

South Asian (SAS)

AF:

0.0254

AC:

122

AN:

4812

European-Finnish (FIN)

AF:

0.0346

AC:

366

AN:

10590

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0260

AC:

1765

AN:

67990

Other (OTH)

AF:

0.0813

AC:

172

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

590

1181

1771

2362

2952

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0496

Hom.:

1208

Bravo

AF:

0.106

Asia WGS

AF:

0.0660

AC:

230

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.8

(source)

DANN

Benign

0.65

PhyloP100

-0.59

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over