4-24800790-T-C

Position:

• chr4-24800790-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003102.4(SOD3):​c.*546T>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 0.0904 in 157,366 control chromosomes in the GnomAD database, including 1,223 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 0.092 (1215 hom., cov: 32)
  • Exomes 𝑓: 0.037 (8 hom.)
• Consequence: SOD3 NM_003102.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.591

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOD3	NM_003102.4	c.*546T>C		3_prime_UTR_variant	2/2	ENST00000382120.4	NP_003093.2
SOD3	XR_427488.2	n.1274T>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOD3	ENST00000382120.4	c.*546T>C		3_prime_UTR_variant	2/2	1	NM_003102.4	ENSP00000371554.3

Frequencies

GnomAD3 genomes AF: 0.0921 AC: 13998 AN: 152020 Hom.: 1205 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0828

Gnomad EAS AF: 0.0478

Gnomad SAS AF: 0.0255

Gnomad FIN AF: 0.0346

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0260

Gnomad OTH AF: 0.0817

GnomAD4 exome AF: 0.0373 AC: 195 AN: 5228 Hom.: 8 Cov.: 0 AF XY: 0.0455 AC XY: 127 AN XY: 2790

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0625

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0374

Gnomad4 NFE exome AF: 0.0265

Gnomad4 OTH exome AF: 0.0517

GnomAD4 genome AF: 0.0923 AC: 14038 AN: 152138 Hom.: 1215 Cov.: 32 AF XY: 0.0934 AC XY: 6943 AN XY: 74374

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.0828

Gnomad4 EAS AF: 0.0479

Gnomad4 SAS AF: 0.0254

Gnomad4 FIN AF: 0.0346

Gnomad4 NFE AF: 0.0260

Gnomad4 OTH AF: 0.0813

Alfa AF: 0.0476 Hom.: 465

Bravo AF: 0.106

Asia WGS AF: 0.0660 AC: 230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.8
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

Other links and lift over

dbSNP: rs8192290; hg19: chr4-24802412;