4-24800212-C-T

Variant names:

• chr4-24800212-C-T
• NM_003102.4:c.691C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003102.4(SOD3):​c.691C>T​(p.Arg231Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000156 in 1,279,206 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: SOD3 NM_003102.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35468304).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD3	NM_003102.4	c.691C>T	p.Arg231Trp	missense_variant	Exon 2 of 2	ENST00000382120.4	NP_003093.2
SOD3	XR_427488.2	n.786C>T		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	c.691C>T	p.Arg231Trp	missense_variant	Exon 2 of 2	1	NM_003102.4	ENSP00000371554.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000156 AC: 2 AN: 1279206 Hom.: 0 Cov.: 35 AF XY: 0.00000318 AC XY: 2 AN XY: 628146

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000194

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.079
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.10
Sift	Benign	0.039	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.28
MutPred		0.18		Loss of methylation at K229 (P = 0.0443);
MVP		0.62
MPC		2.0
ClinPred		0.98	D
GERP RS		1.2
Varity_R		0.22
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-24801834;