12-56002244-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001032386.2(SUOX):​c.23T>C​(p.Val8Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,612,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V8V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SUOX
NM_001032386.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.812

Publications

1 publications found
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 Gene-Disease associations (from GenCC):
  • isolated sulfite oxidase deficiency
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, G2P

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06590867).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SUOXNM_001032386.2 linkc.23T>C p.Val8Ala missense_variant Exon 3 of 5 ENST00000266971.8 NP_001027558.1 P51687A0A024RB79
SUOXNM_000456.3 linkc.23T>C p.Val8Ala missense_variant Exon 4 of 6 NP_000447.2 P51687A0A024RB79
SUOXNM_001032387.2 linkc.23T>C p.Val8Ala missense_variant Exon 2 of 4 NP_001027559.1 P51687A0A024RB79

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SUOXENST00000266971.8 linkc.23T>C p.Val8Ala missense_variant Exon 3 of 5 2 NM_001032386.2 ENSP00000266971.3 P51687

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152188
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00000399
AC:
1
AN:
250392
AF XY:
0.00000738
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1460594
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726698
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.0000756
AC:
3
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52146
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1112002
Other (OTH)
AF:
0.00
AC:
0
AN:
60380
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.408
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152306
Hom.:
0
Cov.:
31
AF XY:
0.0000134
AC XY:
1
AN XY:
74480
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41566
American (AMR)
AF:
0.00
AC:
0
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5190
South Asian (SAS)
AF:
0.000207
AC:
1
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68014
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Sulfite oxidase deficiency Uncertain:1
Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance:Uncertain significance
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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.062
BayesDel_addAF
Benign
-0.045
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
13
DANN
Benign
0.95
DEOGEN2
Benign
0.27
T;T;T;.;.;T;.;.;T
Eigen
Benign
-0.72
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.038
N
LIST_S2
Benign
0.59
.;.;.;T;T;.;T;T;.
M_CAP
Benign
0.047
D
MetaRNN
Benign
0.066
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.37
T
MutationAssessor
Benign
1.4
L;L;L;.;.;L;.;.;L
PhyloP100
0.81
PrimateAI
Benign
0.33
T
PROVEAN
Benign
0.26
N;N;N;D;N;N;N;D;N
REVEL
Benign
0.18
Sift
Benign
0.12
T;T;T;D;T;T;D;D;T
Sift4G
Uncertain
0.031
D;D;D;T;D;D;D;D;D
Polyphen
0.0
B;B;B;B;.;B;.;.;B
Vest4
0.20
MutPred
0.32
Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);
MVP
0.72
MPC
0.16
ClinPred
0.023
T
GERP RS
2.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3
Varity_R
0.026
gMVP
0.55
Mutation Taster
=96/4
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs537720526; hg19: chr12-56396028; API