Variant chr4-24799530-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0970

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 -21 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
SOD3	NM_003102.4 linkuse as main transcript	c.9G>C	p.Ala3=	synonymous_variant	2/2	ENST00000382120.4	NP_003093.2
SOD3	XR_427488.2 linkuse as main transcript	n.104G>C		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOD3	ENST00000382120.4 linkuse as main transcript	c.9G>C	p.Ala3=	synonymous_variant	2/2	1	NM_003102.4	ENSP00000371554	P1
SOD3	ENST00000598411.1 linkuse as main transcript	c.9G>C	p.Ala3=	synonymous_variant	3/3	5		ENSP00000472134

Frequencies

GnomAD3 genomes

AF:

0.0225

AC:

3418

AN:

152190

Hom.:

120

Cov.:

show subpopulations

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.:

AF XY:

0.00466

AC XY:

581

AN XY:

124640

show subpopulations

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.:

AF XY:

0.00241

AC XY:

1738

AN XY:

720288

show subpopulations

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.:

AF XY:

0.0216

AC XY:

1607

AN XY:

74476

show subpopulations

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.:

Bravo

AF:

0.0257

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 24, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over