rs1799895

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003102.4(SOD3):c.691C>G(p.Arg231Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 1,431,336 control chromosomes in the GnomAD database, including 312 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 20 hom., cov: 32)

Exomes 𝑓: 0.016 ( 292 hom. )

Consequence

SOD3
NM_003102.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter P:1B:2

Conservation

PhyloP100: 1.39

Publications

175 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052476227).

BP6

Variant 4-24800212-C-G is Benign according to our data. Variant chr4-24800212-C-G is described in ClinVar as Benign. ClinVar VariationId is 12777.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD3	NM_003102.4 link	c.691C>G	p.Arg231Gly	missense_variant	Exon 2 of 2	ENST00000382120.4	NP_003093.2
SOD3	XR_427488.2 link	n.786C>G		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 link	c.691C>G	p.Arg231Gly	missense_variant	Exon 2 of 2	1	NM_003102.4	ENSP00000371554.3		P08294

Frequencies

GnomAD3 genomes

AF:

0.0127

AC:

1931

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0176

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.0221

Gnomad SAS

AF:

0.0595

Gnomad FIN

AF:

0.0147

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.0124

Gnomad OTH

AF:

0.0167

GnomAD2 exomes

AF:

0.0225

AC:

1116

AN:

49574

AF XY:

0.0242

show subpopulations

Gnomad AFR exome

AF:

0.00138

Gnomad AMR exome

AF:

0.0302

Gnomad ASJ exome

AF:

0.0107

Gnomad EAS exome

AF:

0.0212

Gnomad FIN exome

AF:

0.0164

Gnomad NFE exome

AF:

0.0112

Gnomad OTH exome

AF:

0.0149

GnomAD4 exome

AF:

0.0157

AC:

20136

AN:

1279118

Hom.:

292

Cov.:

AF XY:

0.0168

AC XY:

10556

AN XY:

628084

show subpopulations

African (AFR)

AF:

0.00451

AC:

114

AN:

25302

American (AMR)

AF:

0.0249

AC:

464

AN:

18636

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

250

AN:

20612

East Asian (EAS)

AF:

0.0402

AC:

1108

AN:

27584

South Asian (SAS)

AF:

0.0567

AC:

3606

AN:

63574

European-Finnish (FIN)

AF:

0.0166

AC:

613

AN:

36874

Middle Eastern (MID)

AF:

0.0205

AC:

AN:

3752

European-Non Finnish (NFE)

AF:

0.0127

AC:

13075

AN:

1030098

Other (OTH)

AF:

0.0157

AC:

829

AN:

52686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

1058

2115

3173

4230

5288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

584

1168

1752

2336

2920

<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:

0.0127

AC:

1940

AN:

152218

Hom.:

Cov.:

AF XY:

0.0140

AC XY:

1043

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.00411

AC:

171

AN:

41564

American (AMR)

AF:

0.0176

AC:

269

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0138

AC:

AN:

3470

East Asian (EAS)

AF:

0.0220

AC:

113

AN:

5136

South Asian (SAS)

AF:

0.0592

AC:

286

AN:

4834

European-Finnish (FIN)

AF:

0.0147

AC:

156

AN:

10612

Middle Eastern (MID)

AF:

0.0274

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0124

AC:

843

AN:

67980

Other (OTH)

AF:

0.0218

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

181

272

362

453

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.0112

Hom.:

Bravo

AF:

0.0109

TwinsUK

AF:

0.0135

AC:

ALSPAC

AF:

0.0138

AC:

ExAC

AF:

0.0212

AC:

411

Asia WGS

AF:

0.0470

AC:

165

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SOD3-related disorder

Benign:2

Apr 17, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Jan 05, 2023

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Superoxide dismutase, elevated extracellular

Pathogenic:1

Jan 06, 2004

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0052

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PhyloP100

1.4

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.12

Sift

Uncertain

0.010

Sift4G

Uncertain

0.017

Polyphen

0.067

Vest4

0.12

MPC

1.9

ClinPred

0.046

GERP RS

1.2

Varity_R

0.30

gMVP

0.54

Mutation Taster

=92/8

disease causing (ClinVar)

(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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over