12-55997702-C-T

Position:

chr12-55997702-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.495

Variant links:

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 links:

SUOX (HGNC:):

SUOX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Effect	#exon/exons	MANE	Protein	UniProt
SUOX	NM_001032386.2 linkuse as main transcript	c.-32C>T	5_prime_UTR_variant	2/5	ENST00000266971.8	NP_001027558.1	P51687A0A024RB79
SUOX	NM_000456.3 linkuse as main transcript	c.-158C>T	5_prime_UTR_variant	2/6		NP_000447.2	P51687A0A024RB79
SUOX	NM_001032387.2 linkuse as main transcript	c.-11+363C>T	intron_variant			NP_001027559.1	P51687A0A024RB79

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUOX	ENST00000266971 linkuse as main transcript	c.-32C>T		5_prime_UTR_variant	2/5	2	NM_001032386.2	ENSP00000266971.3		P51687

Frequencies

GnomAD3 genomes

AF:

0.0190

AC:

2888

AN:

152134

Hom.:

Cov.:

show subpopulations

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:

AN:

284

Hom.:

Cov.:

AF XY:

0.0450

AC XY:

AN XY:

222

show subpopulations

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.:

Cov.:

AF XY:

0.0179

AC XY:

1333

AN XY:

74452

show subpopulations

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.:

Bravo

AF:

0.0193

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Sulfite oxidase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over