chr6-159680500-T-G

Variant names:

• chr6-159680500-T-G
• rs10370
• NM_000636.4:c.*1993A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000636.4(SOD2):​c.*1993A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,116 control chromosomes in the GnomAD database, including 4,007 homozygotes. 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 0.22 (4007 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SOD2 NM_000636.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172
• Publications: 20 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD2	NM_000636.4	MANE Select	c.*1993A>C		3_prime_UTR	Exon 5 of 5	NP_000627.2
	SOD2	NM_001322814.2		c.*1993A>C		3_prime_UTR	Exon 4 of 4	NP_001309743.1
	SOD2	NM_001322819.2		c.*1993A>C		3_prime_UTR	Exon 5 of 5	NP_001309748.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD2	ENST00000538183.7	TSL:1 MANE Select	c.*1993A>C		3_prime_UTR	Exon 5 of 5	ENSP00000446252.1
	SOD2	ENST00000367055.8	TSL:1	c.*20-1202A>C		intron	N/A	ENSP00000356022.4
	SOD2	ENST00000546260.5	TSL:5	n.*2366A>C		non_coding_transcript_exon	Exon 5 of 5	ENSP00000440131.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33847 AN: 152000 Hom.: 4003 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.230

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.223 AC: 33864 AN: 152116 Hom.: 4007 Cov.: 32 AF XY: 0.230 AC XY: 17089 AN XY: 74344

African (AFR) AF: 0.150 AC: 6245 AN: 41508

American (AMR) AF: 0.237 AC: 3626 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 696 AN: 3472

East Asian (EAS) AF: 0.402 AC: 2076 AN: 5168

South Asian (SAS) AF: 0.273 AC: 1314 AN: 4820

European-Finnish (FIN) AF: 0.328 AC: 3458 AN: 10544

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15871 AN: 68008

Other (OTH) AF: 0.230 AC: 485 AN: 2112

Alfa AF: 0.220 Hom.: 971

Bravo AF: 0.214

Asia WGS AF: 0.304 AC: 1056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.7
DANN	Benign	0.81
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10370; hg19: chr6-160101532;