NM_000636.4:c.344-23G>T

Variant names:

• chr6-159685056-C-A
• rs2758332
• NM_000636.4:c.344-23G>T

Variant summary

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

The NM_000636.4(SOD2):​c.344-23G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,554,900 control chromosomes in the GnomAD database, including 191,890 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 0.49 (18576 hom., cov: 30)
  • Exomes 𝑓: 0.49 (173314 hom.)
• Consequence: SOD2 NM_000636.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.954
• Publications: 14 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2	NM_000636.4	c.344-23G>T		intron_variant	Intron 3 of 4	ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7	c.344-23G>T		intron_variant	Intron 3 of 4	1	NM_000636.4	ENSP00000446252.1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74131 AN: 151526 Hom.: 18558 Cov.: 30

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.486

GnomAD2 exomes AF: 0.479 AC: 100884 AN: 210598 AF XY: 0.479

Gnomad AFR exome AF: 0.502

Gnomad AMR exome AF: 0.594

Gnomad ASJ exome AF: 0.470

Gnomad EAS exome AF: 0.125

Gnomad FIN exome AF: 0.468

Gnomad NFE exome AF: 0.496

Gnomad OTH exome AF: 0.483

GnomAD4 exome AF: 0.491 AC: 689231 AN: 1403256 Hom.: 173314 Cov.: 27 AF XY: 0.490 AC XY: 341611 AN XY: 696950

African (AFR) AF: 0.508 AC: 15516 AN: 30572

American (AMR) AF: 0.590 AC: 19729 AN: 33456

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 11371 AN: 24200

East Asian (EAS) AF: 0.123 AC: 4790 AN: 38874

South Asian (SAS) AF: 0.518 AC: 40391 AN: 77910

European-Finnish (FIN) AF: 0.479 AC: 24991 AN: 52166

Middle Eastern (MID) AF: 0.448 AC: 2465 AN: 5502

European-Non Finnish (NFE) AF: 0.501 AC: 542487 AN: 1082836

Other (OTH) AF: 0.476 AC: 27491 AN: 57740

GnomAD4 genome AF: 0.489 AC: 74179 AN: 151644 Hom.: 18576 Cov.: 30 AF XY: 0.483 AC XY: 35804 AN XY: 74108

African (AFR) AF: 0.501 AC: 20693 AN: 41266

American (AMR) AF: 0.527 AC: 8032 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1678 AN: 3464

East Asian (EAS) AF: 0.132 AC: 683 AN: 5174

South Asian (SAS) AF: 0.509 AC: 2449 AN: 4810

European-Finnish (FIN) AF: 0.465 AC: 4870 AN: 10478

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34185 AN: 67920

Other (OTH) AF: 0.482 AC: 1009 AN: 2094

Alfa AF: 0.502 Hom.: 4030

Bravo AF: 0.493

Asia WGS AF: 0.350 AC: 1217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.47
DANN	Benign	0.75
PhyloP100		-0.95
Mutation Taster		=29/71	disease causing (long InDel)

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: rs2758332; hg19: chr6-160106088; COSMIC: COSV61622892;