6-159693334-C-G

Variant names:

• chr6-159693334-C-G
• rs5746091
• ENST00000545162.5:c.93-471G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000545162.5(SOD2):​c.93-471G>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 ENST00000545162.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830
• Publications: 4 publications found

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

ACMG classification

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 (BayesDel_noAF=-0.43).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2	NM_000636.4	c.-167G>C		upstream_gene_variant		ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7	c.-167G>C		upstream_gene_variant		1	NM_000636.4	ENSP00000446252.1

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

African (AFR) AF: 0.00 AC: 0 AN: 3320

American (AMR) AF: 0.000312 AC: 1 AN: 3204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3660

East Asian (EAS) AF: 0.00 AC: 0 AN: 9762

South Asian (SAS) AF: 0.000337 AC: 1 AN: 2968

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11458

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 690

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 116560

Other (OTH) AF: 0.000124 AC: 1 AN: 8092

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

African (AFR) AF: 0.0000547 AC: 2 AN: 36550

American (AMR) AF: 0.000141 AC: 2 AN: 14174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3306

East Asian (EAS) AF: 0.000219 AC: 1 AN: 4566

South Asian (SAS) AF: 0.00 AC: 0 AN: 4450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.0000159 AC: 1 AN: 62782

Other (OTH) AF: 0.00 AC: 0 AN: 1884

Alfa AF: 0.00 Hom.: 88

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
PhyloP100		-0.083
PromoterAI		-0.095	Neutral

Splicing

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

Other links and lift over

dbSNP: rs5746091; hg19: chr6-160114366;