12-56001170-A-G

Position:

• chr12-56001170-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUOX	NM_001032386.2	c.-10-1042A>G		intron_variant		ENST00000266971.8	NP_001027558.1
SUOX	NM_000456.3	c.-10-1042A>G		intron_variant			NP_000447.2
SUOX	NM_001032387.2	c.-10-1042A>G		intron_variant			NP_001027559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUOX	ENST00000266971.8	c.-10-1042A>G		intron_variant		2	NM_001032386.2	ENSP00000266971.3

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.500

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

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.396

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.9
DANN	Benign	0.68

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: rs773125; hg19: chr12-56394954;