NM_003102.4:c.172G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_003102.4(SOD3):c.172G>A(p.Ala58Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 1,578,062 control chromosomes in the GnomAD database, including 302,909 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.50 ( 22364 hom., cov: 33)

Exomes 𝑓: 0.62 ( 280545 hom. )

Consequence

SOD3
NM_003102.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.06

Publications

88 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.6705037E-6).

BP6

Variant 4-24799693-G-A is Benign according to our data. Variant chr4-24799693-G-A is described in ClinVar as [Benign]. Clinvar id is 3060834.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD3	NM_003102.4 link	c.172G>A	p.Ala58Thr	missense_variant	Exon 2 of 2	ENST00000382120.4	NP_003093.2
SOD3	XR_427488.2 link	n.267G>A		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.172G>A	p.Ala58Thr	missense_variant	Exon 2 of 2	1	NM_003102.4	ENSP00000371554.3		P08294
SOD3	ENST00000598411.1 link	c.*10G>A		downstream_gene_variant		5		ENSP00000472134.1		M0R1V4

Frequencies

GnomAD3 genomes

AF:

0.502

AC:

76267

AN:

151936

Hom.:

22372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.206

Gnomad AMI

AF:

0.737

Gnomad AMR

AF:

0.478

Gnomad ASJ

AF:

0.602

Gnomad EAS

AF:

0.327

Gnomad SAS

AF:

0.502

Gnomad FIN

AF:

0.753

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.653

Gnomad OTH

AF:

0.520

GnomAD2 exomes

AF:

0.552

AC:

100699

AN:

182560

AF XY:

0.565

show subpopulations

Gnomad AFR exome

AF:

0.195

Gnomad AMR exome

AF:

0.407

Gnomad ASJ exome

AF:

0.610

Gnomad EAS exome

AF:

0.329

Gnomad FIN exome

AF:

0.745

Gnomad NFE exome

AF:

0.661

Gnomad OTH exome

AF:

0.575

GnomAD4 exome

AF:

0.618

AC:

881954

AN:

1426010

Hom.:

280545

Cov.:

AF XY:

0.617

AC XY:

436815

AN XY:

707466

show subpopulations

African (AFR)

AF:

0.187

AC:

6139

AN:

32764

American (AMR)

AF:

0.410

AC:

16576

AN:

40446

Ashkenazi Jewish (ASJ)

AF:

0.614

AC:

15735

AN:

25642

East Asian (EAS)

AF:

0.303

AC:

11403

AN:

37606

South Asian (SAS)

AF:

0.515

AC:

42637

AN:

82746

European-Finnish (FIN)

AF:

0.733

AC:

31582

AN:

43076

Middle Eastern (MID)

AF:

0.549

AC:

3146

AN:

5732

European-Non Finnish (NFE)

AF:

0.655

AC:

720005

AN:

1098786

Other (OTH)

AF:

0.587

AC:

34731

AN:

59212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

21858

43715

65573

87430

109288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.502

AC:

76261

AN:

152052

Hom.:

22364

Cov.:

AF XY:

0.504

AC XY:

37452

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.206

AC:

8543

AN:

41504

American (AMR)

AF:

0.478

AC:

7308

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.602

AC:

2090

AN:

3472

East Asian (EAS)

AF:

0.326

AC:

1677

AN:

5140

South Asian (SAS)

AF:

0.501

AC:

2412

AN:

4816

European-Finnish (FIN)

AF:

0.753

AC:

7986

AN:

10610

Middle Eastern (MID)

AF:

0.469

AC:

137

AN:

292

European-Non Finnish (NFE)

AF:

0.653

AC:

44341

AN:

67898

Other (OTH)

AF:

0.518

AC:

1096

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1652

3304

4955

6607

8259

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.616

Hom.:

54682

Bravo

AF:

0.468

TwinsUK

AF:

0.665

AC:

2466

ALSPAC

AF:

0.666

AC:

2568

ESP6500AA

AF:

0.257

AC:

1082

ESP6500EA

AF:

0.662

AC:

5556

ExAC

AF:

0.519

AC:

58693

Asia WGS

AF:

0.408

AC:

1419

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SOD3-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as 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

0.069

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.054

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.029

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0000017

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.9

PhyloP100

-2.1

PrimateAI

Benign

0.29

PROVEAN

Benign

0.25

REVEL

Benign

0.011

Sift

Benign

0.70

Sift4G

Benign

0.78

Polyphen

0.19

Vest4

0.011

MPC

0.91

ClinPred

0.0032

GERP RS

-1.3

Varity_R

0.066

gMVP

0.66

Mutation Taster

=95/5

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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NM_003102.4:c.172G>A

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