12-56001170-A-G

Variant names:

• chr12-56001170-A-G
• rs773125
• NM_001032386.2:c.-10-1042A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001032386.2(SUOX):​c.-10-1042A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 125,774 control chromosomes in the GnomAD database, including 10,446 homozygotes. 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: 𝑓 0.42 (10445 hom., cov: 18)
  • Exomes 𝑓: 0.21 (1 hom.)
• Consequence: SUOX NM_001032386.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.624
• Publications: 44 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), Ambry Genetics, ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.468 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUOX	NM_001032386.2	MANE Select	c.-10-1042A>G		intron	N/A	NP_001027558.1
	SUOX	NM_000456.3		c.-10-1042A>G		intron	N/A	NP_000447.2
	SUOX	NM_001032387.2		c.-10-1042A>G		intron	N/A	NP_001027559.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUOX	ENST00000266971.8	TSL:2 MANE Select	c.-10-1042A>G		intron	N/A	ENSP00000266971.3
	SUOX	ENST00000356124.8	TSL:1	c.-10-1042A>G		intron	N/A	ENSP00000348440.4
	SUOX	ENST00000552813.5	TSL:1	n.132-1042A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.417 AC: 52363 AN: 125656 Hom.: 10426 Cov.: 18

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.395

GnomAD4 exome AF: 0.206 AC: 7 AN: 34 Hom.: 1 AF XY: 0.208 AC XY: 5 AN XY: 24

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.208 AC: 5 AN: 24

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.417 AC: 52428 AN: 125740 Hom.: 10445 Cov.: 18 AF XY: 0.415 AC XY: 24617 AN XY: 59350

African (AFR) AF: 0.474 AC: 15805 AN: 33332

American (AMR) AF: 0.375 AC: 3992 AN: 10646

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1314 AN: 3268

East Asian (EAS) AF: 0.264 AC: 1007 AN: 3814

South Asian (SAS) AF: 0.289 AC: 1091 AN: 3776

European-Finnish (FIN) AF: 0.420 AC: 2557 AN: 6084

Middle Eastern (MID) AF: 0.438 AC: 84 AN: 192

European-Non Finnish (NFE) AF: 0.409 AC: 25413 AN: 62080

Other (OTH) AF: 0.396 AC: 676 AN: 1708

Alfa AF: 0.382 Hom.: 1192

Bravo AF: 0.393

Asia WGS AF: 0.248 AC: 864 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.9
DANN	Benign	0.68
PhyloP100		-0.62
PromoterAI		-0.019	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs773125; hg19: chr12-56394954;