chr4-24799638-C-T

Variant names:

• chr4-24799638-C-T
• rs141224088
• NM_003102.4:c.117C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_003102.4(SOD3):​c.117C>T​(p.Tyr39Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000658 in 1,605,010 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00069 (1 hom.)
• Consequence: SOD3 NM_003102.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.134
• Publications: 2 publications found

Genes affected

SOD3 (HGNC:11181): (superoxide dismutase 3) This gene encodes a member of the superoxide dismutase (SOD) protein family. SODs are antioxidant enzymes that catalyze the conversion of superoxide radicals into hydrogen peroxide and oxygen, which may protect the brain, lungs, and other tissues from oxidative stress. Proteolytic processing of the encoded protein results in the formation of two distinct homotetramers that differ in their ability to interact with the extracellular matrix (ECM). Homotetramers consisting of the intact protein, or type C subunit, exhibit high affinity for heparin and are anchored to the ECM. Homotetramers consisting of a proteolytically cleaved form of the protein, or type A subunit, exhibit low affinity for heparin and do not interact with the ECM. A mutation in this gene may be associated with increased heart disease risk. [provided by RefSeq, Oct 2015]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 4-24799638-C-T is Benign according to our data. Variant chr4-24799638-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 714475.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.134 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003102.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD3	NM_003102.4	MANE Select	c.117C>T	p.Tyr39Tyr	synonymous	Exon 2 of 2	NP_003093.2	A0A140VJU8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD3	ENST00000382120.4	TSL:1 MANE Select	c.117C>T	p.Tyr39Tyr	synonymous	Exon 2 of 2	ENSP00000371554.3	P08294
	SOD3	ENST00000880265.1		c.117C>T	p.Tyr39Tyr	synonymous	Exon 3 of 3	ENSP00000550324.1
	SOD3	ENST00000952028.1		c.117C>T	p.Tyr39Tyr	synonymous	Exon 3 of 3	ENSP00000622087.1

Frequencies

GnomAD3 genomes AF: 0.000388 AC: 59 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000655 AC: 150 AN: 229140 AF XY: 0.000690

Gnomad AFR exome AF: 0.000218

Gnomad AMR exome AF: 0.000507

Gnomad ASJ exome AF: 0.000103

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000786

Gnomad NFE exome AF: 0.00109

Gnomad OTH exome AF: 0.000524

GnomAD4 exome AF: 0.000686 AC: 997 AN: 1452674 Hom.: 1 Cov.: 31 AF XY: 0.000641 AC XY: 463 AN XY: 722548

African (AFR) AF: 0.0000899 AC: 3 AN: 33378

American (AMR) AF: 0.000361 AC: 16 AN: 44292

Ashkenazi Jewish (ASJ) AF: 0.000154 AC: 4 AN: 25998

East Asian (EAS) AF: 0.00 AC: 0 AN: 39460

South Asian (SAS) AF: 0.00 AC: 0 AN: 85322

European-Finnish (FIN) AF: 0.000604 AC: 29 AN: 48028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.000821 AC: 911 AN: 1110254

Other (OTH) AF: 0.000565 AC: 34 AN: 60184

GnomAD4 genome AF: 0.000387 AC: 59 AN: 152336 Hom.: 0 Cov.: 32 AF XY: 0.000362 AC XY: 27 AN XY: 74494

African (AFR) AF: 0.000216 AC: 9 AN: 41584

American (AMR) AF: 0.000196 AC: 3 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 68020

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000535 Hom.: 0

Bravo AF: 0.000427

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	SOD3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.7
DANN	Benign	0.64
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism

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: rs141224088; hg19: chr4-24801260;