dbSNP rs2855262: SOD3:c.*110T>C (chr4-24800354-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003102.4(SOD3):c.*110T>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 0.61 in 1,150,044 control chromosomes in the GnomAD database, including 222,949 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 0.50 ( 22328 hom., cov: 30)

Exomes 𝑓: 0.63 ( 200621 hom. )

Consequence

SOD3
NM_003102.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.555

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD3	NM_003102.4 link	c.*110T>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000382120.4	NP_003093.2
SOD3	XR_427488.2 link	n.928T>C		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.*110T>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_003102.4	ENSP00000371554.3		P08294

Frequencies

GnomAD3 genomes

AF:

0.500

AC:

75769

AN:

151636

Hom.:

22331

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.805

Gnomad AMR

AF:

0.541

Gnomad ASJ

AF:

0.608

Gnomad EAS

AF:

0.373

Gnomad SAS

AF:

0.514

Gnomad FIN

AF:

0.704

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.651

Gnomad OTH

AF:

0.531

GnomAD4 exome

AF:

0.627

AC:

626093

AN:

998290

Hom.:

200621

Cov.:

AF XY:

0.627

AC XY:

301452

AN XY:

480780

show subpopulations

Gnomad4 AFR exome

AF:

0.152

Gnomad4 AMR exome

AF:

0.515

Gnomad4 ASJ exome

AF:

0.619

Gnomad4 EAS exome

AF:

0.340

Gnomad4 SAS exome

AF:

0.528

Gnomad4 FIN exome

AF:

0.686

Gnomad4 NFE exome

AF:

0.651

Gnomad4 OTH exome

AF:

0.596

GnomAD4 genome

AF:

0.499

AC:

75768

AN:

151754

Hom.:

22328

Cov.:

AF XY:

0.502

AC XY:

37202

AN XY:

74128

show subpopulations

Gnomad4 AFR

AF:

0.179

Gnomad4 AMR

AF:

0.541

Gnomad4 ASJ

AF:

0.608

Gnomad4 EAS

AF:

0.372

Gnomad4 SAS

AF:

0.513

Gnomad4 FIN

AF:

0.704

Gnomad4 NFE

AF:

0.651

Gnomad4 OTH

AF:

0.529

Alfa

AF:

0.590

Hom.:

16526

Bravo

AF:

0.473

Asia WGS

AF:

0.439

AC:

1529

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.5

DANN

Benign

0.65

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over