chr12-56004670-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001032386.2(SUOX):c.1281G>C(p.Ser427Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 1,613,936 control chromosomes in the GnomAD database, including 649,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S427S) has been classified as Benign.

Frequency

Genomes: 𝑓 0.76 ( 48593 hom., cov: 31)

Exomes 𝑓: 0.90 ( 601221 hom. )

Consequence

SUOX
NM_001032386.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.35

Publications

26 publications found

Variant links:

Genes affected

SUOX (HGNC:11460): (sulfite oxidase) Sulfite oxidase is a homodimeric protein localized to the intermembrane space of mitochondria. Each subunit contains a heme domain and a molybdopterin-binding domain. The enzyme catalyzes the oxidation of sulfite to sulfate, the final reaction in the oxidative degradation of the sulfur amino acids cysteine and methionine. Sulfite oxidase deficiency results in neurological abnormalities which are often fatal at an early age. Alternative splicing results in multiple transcript variants encoding identical proteins. [provided by RefSeq, Jul 2008]

SUOX Gene-Disease associations (from GenCC):

isolated sulfite oxidase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, G2P

SUOX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 12-56004670-G-C is Benign according to our data. Variant chr12-56004670-G-C is described in ClinVar as [Benign]. Clinvar id is 130383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.35 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUOX	NM_001032386.2 link	c.1281G>C	p.Ser427Ser	synonymous_variant	Exon 5 of 5	ENST00000266971.8	NP_001027558.1	P51687A0A024RB79
SUOX	NM_000456.3 link	c.1281G>C	p.Ser427Ser	synonymous_variant	Exon 6 of 6		NP_000447.2	P51687A0A024RB79
SUOX	NM_001032387.2 link	c.1281G>C	p.Ser427Ser	synonymous_variant	Exon 4 of 4		NP_001027559.1	P51687A0A024RB79

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUOX	ENST00000266971.8 link	c.1281G>C	p.Ser427Ser	synonymous_variant	Exon 5 of 5	2	NM_001032386.2	ENSP00000266971.3		P51687

Frequencies

GnomAD3 genomes

AF:

0.761

AC:

115565

AN:

151934

Hom.:

48594

Cov.:

show subpopulations

Gnomad AFR

AF:

0.362

Gnomad AMI

AF:

0.911

Gnomad AMR

AF:

0.877

Gnomad ASJ

AF:

0.903

Gnomad EAS

AF:

0.928

Gnomad SAS

AF:

0.943

Gnomad FIN

AF:

0.899

Gnomad MID

AF:

0.917

Gnomad NFE

AF:

0.917

Gnomad OTH

AF:

0.833

GnomAD2 exomes

AF:

0.884

AC:

222277

AN:

251404

AF XY:

0.895

show subpopulations

Gnomad AFR exome

AF:

0.349

Gnomad AMR exome

AF:

0.933

Gnomad ASJ exome

AF:

0.907

Gnomad EAS exome

AF:

0.933

Gnomad FIN exome

AF:

0.900

Gnomad NFE exome

AF:

0.916

Gnomad OTH exome

AF:

0.898

GnomAD4 exome

AF:

0.903

AC:

1319436

AN:

1461884

Hom.:

601221

Cov.:

AF XY:

0.906

AC XY:

658553

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.343

AC:

11496

AN:

33480

American (AMR)

AF:

0.926

AC:

41408

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.909

AC:

23745

AN:

26136

East Asian (EAS)

AF:

0.942

AC:

37397

AN:

39700

South Asian (SAS)

AF:

0.943

AC:

81311

AN:

86258

European-Finnish (FIN)

AF:

0.900

AC:

48102

AN:

53420

Middle Eastern (MID)

AF:

0.908

AC:

5239

AN:

5768

European-Non Finnish (NFE)

AF:

0.915

AC:

1017339

AN:

1112002

Other (OTH)

AF:

0.884

AC:

53399

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

8301

16601

24902

33202

41503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.760

AC:

115585

AN:

152052

Hom.:

48593

Cov.:

AF XY:

0.766

AC XY:

56899

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.362

AC:

14982

AN:

41402

American (AMR)

AF:

0.877

AC:

13400

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.903

AC:

3132

AN:

3468

East Asian (EAS)

AF:

0.929

AC:

4794

AN:

5162

South Asian (SAS)

AF:

0.943

AC:

4552

AN:

4826

European-Finnish (FIN)

AF:

0.899

AC:

9520

AN:

10584

Middle Eastern (MID)

AF:

0.911

AC:

266

AN:

292

European-Non Finnish (NFE)

AF:

0.917

AC:

62353

AN:

68018

Other (OTH)

AF:

0.832

AC:

1757

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

966

1932

2899

3865

4831

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.838

Hom.:

6589

Bravo

AF:

0.745

EpiCase

AF:

0.916

EpiControl

AF:

0.913

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Sulfite oxidase deficiency

Benign:5

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 23, 2017

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 98% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 91. Only high quality variants are reported. -

Dec 03, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.20

(source)

DANN

Benign

0.65

PhyloP100

-1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=86/14

disease causing (ClinVar)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr12-56004670-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over