Genetic Variant SOD2:p.Val142Ile (chr6-159684953-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000636.4(SOD2):c.424G>A(p.Val142Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V142F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SOD2
NM_000636.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.90

Publications

0 publications found

Variant links:

Genes affected

SOD2 (HGNC:11180): (superoxide dismutase 2) This gene is a member of the iron/manganese superoxide dismutase family. It encodes a mitochondrial protein that forms a homotetramer and binds one manganese ion per subunit. This protein binds to the superoxide byproducts of oxidative phosphorylation and converts them to hydrogen peroxide and diatomic oxygen. Mutations in this gene have been associated with idiopathic cardiomyopathy (IDC), premature aging, sporadic motor neuron disease, and cancer. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 1. [provided by RefSeq, Apr 2016]

SOD2 Gene-Disease associations (from GenCC):

microvascular complications of diabetes, susceptibility to, 6
Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia
cardiomyopathy
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
dilated cardiomyopathy
Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

SOD2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23204094).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000636.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SOD2	NM_000636.4	MANE Select	c.424G>A	p.Val142Ile	missense	Exon 4 of 5	NP_000627.2	P04179-1
SOD2	NM_001024465.3		c.424G>A	p.Val142Ile	missense	Exon 4 of 6	NP_001019636.1	P04179-1
SOD2	NM_001024466.3		c.307G>A	p.Val103Ile	missense	Exon 3 of 5	NP_001019637.1	P04179-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SOD2	ENST00000538183.7	TSL:1 MANE Select	c.424G>A	p.Val142Ile	missense	Exon 4 of 5	ENSP00000446252.1	P04179-1
SOD2	ENST00000367055.8	TSL:1	c.424G>A	p.Val142Ile	missense	Exon 4 of 6	ENSP00000356022.4	P04179-1
SOD2	ENST00000881541.1		c.421G>A	p.Val141Ile	missense	Exon 4 of 5	ENSP00000551600.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.076

Eigen

Benign

-0.086

Eigen_PC

Benign

0.013

FATHMM_MKL

Uncertain

0.87

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.0082

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.89

PhyloP100

5.9

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.45

REVEL

Benign

0.11

Sift

Benign

0.39

Sift4G

Benign

0.96

Polyphen

0.67

Vest4

0.27

MutPred

0.44

Gain of sheet (P = 0.1451)

MVP

0.46

MPC

0.40

ClinPred

0.88

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.088

gMVP

0.48

Mutation Taster

=59/41

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over