12-56004670-G-C

Variant names:

• chr12-56004670-G-C
• rs773115
• NM_001032386.2:c.1281G>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -1.35
• Publications: 26 publications found

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), G2P, PanelApp Australia, Ambry Genetics, ClinGen

ACMG classification

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001032386.2. 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
	SUOX	NM_001032386.2	MANE Select	c.1281G>C	p.Ser427Ser	synonymous	Exon 5 of 5	NP_001027558.1	P51687
	SUOX	NM_000456.3		c.1281G>C	p.Ser427Ser	synonymous	Exon 6 of 6	NP_000447.2	P51687
	SUOX	NM_001032387.2		c.1281G>C	p.Ser427Ser	synonymous	Exon 4 of 4	NP_001027559.1	P51687

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUOX	ENST00000266971.8	TSL:2 MANE Select	c.1281G>C	p.Ser427Ser	synonymous	Exon 5 of 5	ENSP00000266971.3	P51687
	SUOX	ENST00000356124.8	TSL:1	c.1281G>C	p.Ser427Ser	synonymous	Exon 4 of 4	ENSP00000348440.4	P51687
	SUOX	ENST00000394109.7	TSL:1	c.1281G>C	p.Ser427Ser	synonymous	Exon 3 of 3	ENSP00000377668.3	P51687

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115565 AN: 151934 Hom.: 48594 Cov.: 31

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

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.: 72 AF XY: 0.906 AC XY: 658553 AN XY: 727244

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

GnomAD4 genome AF: 0.760 AC: 115585 AN: 152052 Hom.: 48593 Cov.: 31 AF XY: 0.766 AC XY: 56899 AN XY: 74298

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

Alfa AF: 0.838 Hom.: 6589

Bravo AF: 0.745

EpiCase AF: 0.916

EpiControl AF: 0.913

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	Sulfite oxidase deficiency (5)
-	-	4	not specified (4)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.20
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)

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: rs773115; hg19: chr12-56398454; COSMIC: COSV108027526; COSMIC: COSV108027526;