rs773126

Variant names:

• chr12-56001636-T-A
• rs773126
• ENST00000394109.7:c.-586T>A

Your query was ambiguous. Multiple possible variants found:

• chr12-56001636-T-A
• chr12-56001636-T-G

Variant summary

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

The ENST00000394109.7(SUOX):​c.-586T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 169,990 control chromosomes in the GnomAD database, including 13,036 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 0.37 (11556 hom., cov: 31)
  • Exomes 𝑓: 0.37 (1480 hom.)
• Consequence: SUOX ENST00000394109.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.594
• Publications: 2 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=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000394109.7. 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.-10-576T>A		intron	N/A	NP_001027558.1
	SUOX	NM_000456.3		c.-10-576T>A		intron	N/A	NP_000447.2
	SUOX	NM_001032387.2		c.-10-576T>A		intron	N/A	NP_001027559.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUOX	ENST00000394109.7	TSL:1	c.-586T>A		5_prime_UTR	Exon 1 of 3	ENSP00000377668.3
	SUOX	ENST00000266971.8	TSL:2 MANE Select	c.-10-576T>A		intron	N/A	ENSP00000266971.3
	SUOX	ENST00000356124.8	TSL:1	c.-10-576T>A		intron	N/A	ENSP00000348440.4

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56302 AN: 151842 Hom.: 11554 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.0120

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.390

GnomAD4 exome AF: 0.368 AC: 6639 AN: 18030 Hom.: 1480 Cov.: 1 AF XY: 0.361 AC XY: 3293 AN XY: 9122

African (AFR) AF: 0.236 AC: 51 AN: 216

American (AMR) AF: 0.293 AC: 840 AN: 2868

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 83 AN: 206

East Asian (EAS) AF: 0.00703 AC: 8 AN: 1138

South Asian (SAS) AF: 0.278 AC: 558 AN: 2006

European-Finnish (FIN) AF: 0.384 AC: 166 AN: 432

Middle Eastern (MID) AF: 0.579 AC: 22 AN: 38

European-Non Finnish (NFE) AF: 0.442 AC: 4556 AN: 10306

Other (OTH) AF: 0.433 AC: 355 AN: 820

GnomAD4 genome AF: 0.371 AC: 56317 AN: 151960 Hom.: 11556 Cov.: 31 AF XY: 0.366 AC XY: 27213 AN XY: 74290

African (AFR) AF: 0.256 AC: 10607 AN: 41422

American (AMR) AF: 0.349 AC: 5332 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1629 AN: 3470

East Asian (EAS) AF: 0.0120 AC: 62 AN: 5176

South Asian (SAS) AF: 0.266 AC: 1284 AN: 4824

European-Finnish (FIN) AF: 0.430 AC: 4534 AN: 10556

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.465 AC: 31584 AN: 67936

Other (OTH) AF: 0.386 AC: 812 AN: 2106

Alfa AF: 0.287 Hom.: 802

Bravo AF: 0.356

Asia WGS AF: 0.139 AC: 483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.8
DANN	Benign	0.74
PhyloP100		0.59
PromoterAI		0.078	Neutral
Mutation Taster		=293/7	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: rs773126; hg19: chr12-56395420;