Variant rs1799895 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.013 ( 20 hom., cov: 32)

Exomes 𝑓: 0.016 ( 292 hom. )

Consequence

SOD3
NM_003102.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity no assertion criteria provided P:1B:1

Conservation

PhyloP100: 1.39

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

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

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

GnomAD3 exomes

AF:

0.0225

AC:

1116

AN:

49574

Hom.:

AF XY:

0.0242

AC XY:

691

AN XY:

28594

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 SAS exome

AF:

0.0534

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

Gnomad4 AFR exome

AF:

0.00451

Gnomad4 AMR exome

AF:

0.0249

Gnomad4 ASJ exome

AF:

0.0121

Gnomad4 EAS exome

AF:

0.0402

Gnomad4 SAS exome

AF:

0.0567

Gnomad4 FIN exome

AF:

0.0166

Gnomad4 NFE exome

AF:

0.0127

Gnomad4 OTH exome

AF:

0.0157

GnomAD4 genome

AF:

0.0127

AC:

1940

AN:

152218

Hom.:

Cov.:

AF XY:

0.0140

AC XY:

1043

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00411

Gnomad4 AMR

AF:

0.0176

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.0220

Gnomad4 SAS

AF:

0.0592

Gnomad4 FIN

AF:

0.0147

Gnomad4 NFE

AF:

0.0124

Gnomad4 OTH

AF:

0.0218

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: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Superoxide dismutase, elevated extracellular

Pathogenic:1

Jan 06, 2004

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

SOD3-related disorder

Benign:1

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). -

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

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

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over