rs76537761

Positions:

chr12-56004747-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP4_StrongBP6_Very_StrongBS2

The NM_001032386.2(SUOX):c.1358G>A(p.Gly453Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0049 in 1,614,140 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 33 hom. )

Consequence

SUOX
NM_001032386.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 8.83

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 7: BayesDel_noAF, Cadd, Eigen, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.026873618).

BP6

Variant 12-56004747-G-A is Benign according to our data. Variant chr12-56004747-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 212329.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-56004747-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SUOX	NM_001032386.2 linkuse as main transcript	c.1358G>A	p.Gly453Asp	missense_variant	5/5	ENST00000266971.8	NP_001027558.1
SUOX	NM_000456.3 linkuse as main transcript	c.1358G>A	p.Gly453Asp	missense_variant	6/6		NP_000447.2
SUOX	NM_001032387.2 linkuse as main transcript	c.1358G>A	p.Gly453Asp	missense_variant	4/4		NP_001027559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUOX	ENST00000266971.8 linkuse as main transcript	c.1358G>A	p.Gly453Asp	missense_variant	5/5	2	NM_001032386.2	ENSP00000266971	P1

Frequencies

GnomAD3 genomes

AF:

0.00373

AC:

567

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00167

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00587

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00379

AC:

953

AN:

251378

Hom.:

AF XY:

0.00369

AC XY:

501

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.0100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000751

Gnomad FIN exome

AF:

0.000786

Gnomad NFE exome

AF:

0.00592

Gnomad OTH exome

AF:

0.00473

GnomAD4 exome

AF:

0.00502

AC:

7345

AN:

1461848

Hom.:

Cov.:

AF XY:

0.00492

AC XY:

3577

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00137

Gnomad4 AMR exome

AF:

0.00253

Gnomad4 ASJ exome

AF:

0.0101

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000939

Gnomad4 FIN exome

AF:

0.000880

Gnomad4 NFE exome

AF:

0.00587

Gnomad4 OTH exome

AF:

0.00444

GnomAD4 genome

AF:

0.00372

AC:

567

AN:

152292

Hom.:

Cov.:

AF XY:

0.00334

AC XY:

249

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00587

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00566

Hom.:

Bravo

AF:

0.00378

TwinsUK

AF:

0.00836

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.00640

AC:

ExAC

AF:

0.00360

AC:

437

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00632

EpiControl

AF:

0.00622

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 12, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 23, 2021	- -

Sulfite oxidase deficiency

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

SUOX-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 29, 2021

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.88

D;D;D;D;D

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.99

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.027

T;T;T;T;T

MetaSVM

Uncertain

0.50

MutationAssessor

Pathogenic

3.1

M;M;M;M;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-6.7

D;D;D;D;D

REVEL

Pathogenic

0.83

Sift

Uncertain

0.0020

D;D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D;D

Polyphen

1.0

D;D;D;D;D

Vest4

0.78

MVP

0.90

MPC

0.65

ClinPred

0.036

GERP RS

5.0

Varity_R

0.87

gMVP

0.91

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over