chr6-159682083-G-T

Variant names:

• chr6-159682083-G-T
• rs5746134
• NM_000636.4:c.*410C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000636.4(SOD2):​c.*410C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000602 in 1,660 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: not found (cov: 32)
  • Exomes 𝑓: 0.00060 (0 hom.)
• Consequence: SOD2 NM_000636.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388
• Publications: 8 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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.*410C>A		3_prime_UTR	Exon 5 of 5	NP_000627.2
	SOD2	NM_001322814.2		c.*410C>A		3_prime_UTR	Exon 4 of 4	NP_001309743.1
	SOD2	NM_001322819.2		c.*410C>A		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.*410C>A		3_prime_UTR	Exon 5 of 5	ENSP00000446252.1
	SOD2	ENST00000367055.8	TSL:1	c.*19+391C>A		intron	N/A	ENSP00000356022.4
	SOD2	ENST00000546260.5	TSL:5	n.*783C>A		non_coding_transcript_exon	Exon 5 of 5	ENSP00000440131.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.000602 AC: 1 AN: 1660 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 862

African (AFR) AF: 0.00 AC: 0 AN: 38

American (AMR) AF: 0.0152 AC: 1 AN: 66

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 50

East Asian (EAS) AF: 0.00 AC: 0 AN: 28

South Asian (SAS) AF: 0.00 AC: 0 AN: 236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110

Other (OTH) AF: 0.00 AC: 0 AN: 88

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 409

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.59
PhyloP100		-0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs5746134; hg19: chr6-160103115;