rs7963590

Positions:

• chr12-56001905-G-A
• chr12-56001905-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001032386.2(SUOX):​c.-10-307G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 1,255,350 control chromosomes in the GnomAD database, including 3,838 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 0.068 (400 hom., cov: 31)
  • Exomes 𝑓: 0.077 (3438 hom.)
• Consequence: SUOX NM_001032386.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUOX	NM_001032386.2	c.-10-307G>A		intron_variant		ENST00000266971.8	NP_001027558.1
SUOX	NM_000456.3	c.-10-307G>A		intron_variant			NP_000447.2
SUOX	NM_001032387.2	c.-10-307G>A		intron_variant			NP_001027559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUOX	ENST00000266971.8	c.-10-307G>A		intron_variant		2	NM_001032386.2	ENSP00000266971	P1

Frequencies

GnomAD3 genomes AF: 0.0685 AC: 10416 AN: 152066 Hom.: 400 Cov.: 31

Gnomad AFR AF: 0.0626

Gnomad AMI AF: 0.0879

Gnomad AMR AF: 0.0453

Gnomad ASJ AF: 0.0740

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0537

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0784

Gnomad OTH AF: 0.0569

GnomAD4 exome AF: 0.0768 AC: 84750 AN: 1103166 Hom.: 3438 Cov.: 30 AF XY: 0.0761 AC XY: 40182 AN XY: 528212

Gnomad4 AFR exome AF: 0.0645

Gnomad4 AMR exome AF: 0.0402

Gnomad4 ASJ exome AF: 0.0701

Gnomad4 EAS exome AF: 0.000267

Gnomad4 SAS exome AF: 0.0538

Gnomad4 FIN exome AF: 0.0943

Gnomad4 NFE exome AF: 0.0807

Gnomad4 OTH exome AF: 0.0712

GnomAD4 genome AF: 0.0685 AC: 10418 AN: 152184 Hom.: 400 Cov.: 31 AF XY: 0.0691 AC XY: 5140 AN XY: 74408

Gnomad4 AFR AF: 0.0625

Gnomad4 AMR AF: 0.0452

Gnomad4 ASJ AF: 0.0740

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0535

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.0785

Gnomad4 OTH AF: 0.0559

Alfa AF: 0.0418 Hom.: 39

Bravo AF: 0.0635

Asia WGS AF: 0.0220 AC: 75 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.2
DANN	Benign	0.62

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

Other links and lift over

dbSNP: rs7963590; hg19: chr12-56395689;