4-24799732-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_003102.4(SOD3):c.211C>T(p.Leu71=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,561,880 control chromosomes in the GnomAD database, including 30,931 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2431 hom., cov: 33)
  • Exomes 𝑓: 0.20 (28500 hom.)
• Consequence: SOD3 NM_003102.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.41

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 4-24799732-C-T is Benign according to our data. Variant chr4-24799732-C-T is described in ClinVar as [Benign]. Clinvar id is 3060611.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.41 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOD3	NM_003102.4	c.211C>T	p.Leu71=	synonymous_variant	2/2	ENST00000382120.4
SOD3	XR_427488.2	n.306C>T		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOD3	ENST00000382120.4	c.211C>T	p.Leu71=	synonymous_variant	2/2	1	NM_003102.4	P1
SOD3	ENST00000598411.1			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26238 AN: 152022 Hom.: 2428 Cov.: 33

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.183

GnomAD3 exomes AF: 0.196 AC: 31238 AN: 159278 Hom.: 3229 AF XY: 0.197 AC XY: 17459 AN XY: 88404

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.164

Gnomad ASJ exome AF: 0.179

Gnomad EAS exome AF: 0.372

Gnomad SAS exome AF: 0.204

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.193

Gnomad OTH exome AF: 0.195

GnomAD4 exome AF: 0.197 AC: 277747 AN: 1409744 Hom.: 28500 Cov.: 39 AF XY: 0.198 AC XY: 137862 AN XY: 698034

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.180

Gnomad4 EAS exome AF: 0.414

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.142

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.194

GnomAD4 genome AF: 0.172 AC: 26239 AN: 152136 Hom.: 2431 Cov.: 33 AF XY: 0.171 AC XY: 12690 AN XY: 74370

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.187

Alfa AF: 0.179 Hom.: 553

Bravo AF: 0.175

Asia WGS AF: 0.257 AC: 891 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SOD3-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

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
BayesDel_noAF	Benign	-0.77
Cadd	Benign	7.7
Dann	Benign	0.96

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

Other links and lift over

dbSNP: rs8192291; hg19: chr4-24801354; COSMIC: COSV66125582; COSMIC: COSV66125582;