Genetic Variant SOD3:p.Ser31Ser (chr4-24799614-G-A) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_003102.4(SOD3):c.93G>A(p.Ser31Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,604,654 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00064 ( 10 hom. )

Consequence

SOD3
NM_003102.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.793

Publications

2 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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 4-24799614-G-A is Benign according to our data. Variant chr4-24799614-G-A is described in ClinVar as [Benign]. Clinvar id is 713304.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.793 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00516 (786/152294) while in subpopulation AFR AF = 0.018 (749/41574). AF 95% confidence interval is 0.0169. There are 5 homozygotes in GnomAd4. There are 372 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD3	NM_003102.4 link	c.93G>A	p.Ser31Ser	synonymous_variant	Exon 2 of 2	ENST00000382120.4	NP_003093.2
SOD3	XR_427488.2 link	n.188G>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.93G>A	p.Ser31Ser	synonymous_variant	Exon 2 of 2	1	NM_003102.4	ENSP00000371554.3		P08294
SOD3	ENST00000598411.1 link	c.93G>A	p.Ser31Ser	synonymous_variant	Exon 3 of 3	5		ENSP00000472134.1		M0R1V4

Frequencies

GnomAD3 genomes

AF:

0.00514

AC:

782

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0180

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00148

AC:

341

AN:

230398

AF XY:

0.00114

show subpopulations

Gnomad AFR exome

AF:

0.0183

Gnomad AMR exome

AF:

0.00137

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00156

GnomAD4 exome

AF:

0.000638

AC:

926

AN:

1452360

Hom.:

Cov.:

AF XY:

0.000559

AC XY:

404

AN XY:

722474

show subpopulations

African (AFR)

AF:

0.0191

AC:

638

AN:

33406

American (AMR)

AF:

0.00174

AC:

AN:

44348

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25990

East Asian (EAS)

AF:

0.00

AC:

AN:

39520

South Asian (SAS)

AF:

0.000562

AC:

AN:

85402

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47250

Middle Eastern (MID)

AF:

0.000869

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000522

AC:

AN:

1110516

Other (OTH)

AF:

0.00166

AC:

100

AN:

60172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

118

178

237

296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00516

AC:

786

AN:

152294

Hom.:

Cov.:

AF XY:

0.00500

AC XY:

372

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0180

AC:

749

AN:

41574

American (AMR)

AF:

0.00170

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68012

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

128

170

213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00145

Hom.:

Bravo

AF:

0.00634

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.9

(source)

DANN

Benign

0.79

PhyloP100

-0.79

Mutation Taster

=100/0

polymorphism

(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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chr4-24799614-G-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