chr12-55997702-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 38 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUOX	NM_001032386.2	MANE Select	c.-32C>T		5_prime_UTR	Exon 2 of 5	NP_001027558.1	P51687
	SUOX	NM_000456.3		c.-158C>T		5_prime_UTR	Exon 2 of 6	NP_000447.2	P51687
	SUOX	NM_001032387.2		c.-11+363C>T		intron	N/A	NP_001027559.1	P51687

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUOX	ENST00000266971.8	TSL:2 MANE Select	c.-32C>T		5_prime_UTR	Exon 2 of 5	ENSP00000266971.3	P51687
	SUOX	ENST00000356124.8	TSL:1	c.-11+363C>T		intron	N/A	ENSP00000348440.4	P51687
	SUOX	ENST00000552813.5	TSL:1	n.110C>T		non_coding_transcript_exon	Exon 2 of 4

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

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

American (AMR) AF: 0.00 AC: 0 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0466 AC: 11 AN: 236

Other (OTH) AF: 0.00 AC: 0 AN: 16

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

African (AFR) AF: 0.00515 AC: 214 AN: 41546

American (AMR) AF: 0.0188 AC: 288 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00746 AC: 36 AN: 4824

European-Finnish (FIN) AF: 0.0173 AC: 184 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0297 AC: 2022 AN: 68016

Other (OTH) AF: 0.0137 AC: 29 AN: 2112

Alfa AF: 0.0258 Hom.: 78

Bravo AF: 0.0193

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Sulfite oxidase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.1
DANN	Benign	0.73
PhyloP100		-0.49
PromoterAI		-0.053	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism

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: rs705703; hg19: chr12-56391486;