12-55997702-C-T

Variant names:

• chr12-55997702-C-T
• rs705703
• NM_001032386.2:c.-32C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001032386.2(SUOX):​c.-32C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 152,536 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (38 hom., cov: 31)
  • Exomes 𝑓: 0.039 (1 hom.)
• Consequence: SUOX NM_001032386.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.495

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 12-55997702-C-T is Benign according to our data. Variant chr12-55997702-C-T is described in ClinVar as [Benign]. Clinvar id is 309824.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.019 (2888/152252) while in subpopulation NFE AF= 0.0297 (2022/68016). AF 95% confidence interval is 0.0286. There are 38 homozygotes in gnomad4. There are 1333 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUOX	NM_001032386.2	c.-32C>T		5_prime_UTR_variant	Exon 2 of 5	ENST00000266971.8	NP_001027558.1
SUOX	NM_000456.3	c.-158C>T		5_prime_UTR_variant	Exon 2 of 6		NP_000447.2
SUOX	NM_001032387.2	c.-11+363C>T		intron_variant	Intron 1 of 3		NP_001027559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUOX	ENST00000266971	c.-32C>T		5_prime_UTR_variant	Exon 2 of 5	2	NM_001032386.2	ENSP00000266971.3

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2888 AN: 152134 Hom.: 38 Cov.: 31

Gnomad AFR AF: 0.00517

Gnomad AMI AF: 0.0540

Gnomad AMR AF: 0.0189

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00746

Gnomad FIN AF: 0.0173

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0297

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.0387 AC: 11 AN: 284 Hom.: 1 Cov.: 0 AF XY: 0.0450 AC XY: 10 AN XY: 222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0466

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0190 AC: 2888 AN: 152252 Hom.: 38 Cov.: 31 AF XY: 0.0179 AC XY: 1333 AN XY: 74452

Gnomad4 AFR AF: 0.00515

Gnomad4 AMR AF: 0.0188

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00746

Gnomad4 FIN AF: 0.0173

Gnomad4 NFE AF: 0.0297

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0265 Hom.: 57

Bravo AF: 0.0193

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Sulfite oxidase deficiency Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.1
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs705703; hg19: chr12-56391486;