6-159693334-C-G

Position:

• chr6-159693334-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001322817.2(SOD2):​c.-115-471G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000303 in 296,574 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: 𝑓 0.000044 (0 hom., cov: 23)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: SOD2 NM_001322817.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BS2: High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOD2	NM_001322817.2	c.-115-471G>C		intron_variant			NP_001309746.1
SOD2	NM_001322819.2	c.-115-471G>C		intron_variant			NP_001309748.1
SOD2	NM_001322820.2	c.-115-471G>C		intron_variant			NP_001309749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000545162.5	c.93-471G>C		intron_variant		3		ENSP00000441362.1
SOD2	ENST00000535561.5	c.93-471G>C		intron_variant		3		ENSP00000445015.1
SOD2	ENST00000546087.5	c.-115-471G>C		intron_variant		2		ENSP00000442920.1

Frequencies

GnomAD3 genomes AF: 0.0000438 AC: 6 AN: 136860 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000547

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000141

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000219

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000159

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000188 AC: 3 AN: 159714 Hom.: 0 Cov.: 4 AF XY: 0.0000242 AC XY: 2 AN XY: 82706

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000312

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000337

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000124

GnomAD4 genome AF: 0.0000438 AC: 6 AN: 136860 Hom.: 0 Cov.: 23 AF XY: 0.0000452 AC XY: 3 AN XY: 66312

Gnomad4 AFR AF: 0.0000547

Gnomad4 AMR AF: 0.000141

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000219

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000159

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	8.3
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5746091; hg19: chr6-160114366;