6-159692840-A-C

Variant names:

• chr6-159692840-A-C
• NM_000636.4:c.47T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000636.4(SOD2):​c.47T>G​(p.Val16Gly) 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. 12/20 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: 𝑓 0.0 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SOD2 NM_000636.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10995099).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2	NM_000636.4	c.47T>G	p.Val16Gly	missense_variant	Exon 2 of 5	ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7	c.47T>G	p.Val16Gly	missense_variant	Exon 2 of 5	1	NM_000636.4	ENSP00000446252.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151888 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 48

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151888 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74170

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.033	.;.;.;.;.;T;T;T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.020	.;T;.;T;T;T;T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.11	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.0	N;N;N;N;N;N;N;N
REVEL	Benign	0.050
Sift	Benign	0.19	T;T;T;T;T;T;D;T
Sift4G	Benign	0.22	T;T;T;T;T;.;.;T
Polyphen		0.84	.;.;.;.;.;.;.;P
Vest4		0.12
MutPred		0.54		Loss of stability (P = 0.0084);Loss of stability (P = 0.0084);Loss of stability (P = 0.0084);Loss of stability (P = 0.0084);Loss of stability (P = 0.0084);.;.;Loss of stability (P = 0.0084);
MVP		0.21
MPC		0.61
ClinPred		0.14	T
GERP RS		3.1
Varity_R		0.068
gMVP		0.33

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: chr6-160113872;