4-24799530-G-C

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.9G>C(p.Ala3=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00454 in 1,599,408 control chromosomes in the GnomAD database, including 237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (119 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (118 hom.)
• Consequence: SOD3 NM_003102.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0970

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=-0.63).
• BP6: Variant 4-24799530-G-C is Benign according to our data. Variant chr4-24799530-G-C is described in ClinVar as [Benign]. Clinvar id is 775951.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.097 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOD3	NM_003102.4	c.9G>C	p.Ala3=	synonymous_variant	2/2	ENST00000382120.4
SOD3	XR_427488.2	n.104G>C		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOD3	ENST00000382120.4	c.9G>C	p.Ala3=	synonymous_variant	2/2	1	NM_003102.4	P1
SOD3	ENST00000598411.1	c.9G>C	p.Ala3=	synonymous_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 3418 AN: 152190 Hom.: 120 Cov.: 33

Gnomad AFR AF: 0.0749

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0135

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.0225

GnomAD3 exomes AF: 0.00586 AC: 1319 AN: 224946 Hom.: 46 AF XY: 0.00466 AC XY: 581 AN XY: 124640

Gnomad AFR exome AF: 0.0758

Gnomad AMR exome AF: 0.00542

Gnomad ASJ exome AF: 0.000104

Gnomad EAS exome AF: 0.000515

Gnomad SAS exome AF: 0.000135

Gnomad FIN exome AF: 0.0000792

Gnomad NFE exome AF: 0.000566

Gnomad OTH exome AF: 0.00456

GnomAD4 exome AF: 0.00266 AC: 3850 AN: 1447100 Hom.: 118 Cov.: 31 AF XY: 0.00241 AC XY: 1738 AN XY: 720288

Gnomad4 AFR exome AF: 0.0770

Gnomad4 AMR exome AF: 0.00636

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.000252

Gnomad4 SAS exome AF: 0.000245

Gnomad4 FIN exome AF: 0.0000738

Gnomad4 NFE exome AF: 0.000460

Gnomad4 OTH exome AF: 0.00660

GnomAD4 genome AF: 0.0224 AC: 3412 AN: 152308 Hom.: 119 Cov.: 33 AF XY: 0.0216 AC XY: 1607 AN XY: 74476

Gnomad4 AFR AF: 0.0746

Gnomad4 AMR AF: 0.0135

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000662

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.00163 Hom.: 7

Bravo AF: 0.0257

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 24, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	12
Dann	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs17882667; hg19: chr4-24801152;