6-159692858-C-T

Variant summary

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

The NM_000636.4(SOD2):​c.29G>A​(p.Ser10Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SOD2
NM_000636.4 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.75

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):
  • cardiomyopathy
    Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

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=0.14130178).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SOD2NM_000636.4 linkc.29G>A p.Ser10Asn missense_variant Exon 2 of 5 ENST00000538183.7 NP_000627.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SOD2ENST00000538183.7 linkc.29G>A p.Ser10Asn missense_variant Exon 2 of 5 1 NM_000636.4 ENSP00000446252.1 P04179-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1453444
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
722688
African (AFR)
AF:
0.00
AC:
0
AN:
33332
American (AMR)
AF:
0.00
AC:
0
AN:
43542
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25858
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39488
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85442
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51164
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5634
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1108882
Other (OTH)
AF:
0.00
AC:
0
AN:
60102
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.094
T;T;.;.;.;T;T;T
Eigen
Benign
-0.50
Eigen_PC
Benign
-0.53
FATHMM_MKL
Benign
0.49
N
LIST_S2
Benign
0.72
.;T;.;T;T;T;T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.14
T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L;L;L;L;L;.;.;.
PhyloP100
1.7
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-1.1
N;N;N;N;N;N;N;N
REVEL
Benign
0.032
Sift
Benign
0.11
T;T;T;T;T;D;T;D
Sift4G
Benign
0.090
T;T;T;T;T;.;.;D
Polyphen
0.13
B;B;.;.;.;.;.;D
Vest4
0.12
MutPred
0.39
Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);.;.;Gain of relative solvent accessibility (P = 0.0479);
MVP
0.42
MPC
0.43
ClinPred
0.15
T
GERP RS
3.0
PromoterAI
0.018
Neutral
Varity_R
0.18
gMVP
0.35
Mutation Taster
=96/4
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs5746096; hg19: chr6-160113890; API