12-56002240-G-A

Position:

chr12-56002240-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_001032386.2(SUOX):c.19G>A(p.Ala7Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000577 in 1,612,818 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000060 ( 1 hom. )

Consequence

SUOX
NM_001032386.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.0680

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 Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05502677).

BP6

Variant 12-56002240-G-A is Benign according to our data. Variant chr12-56002240-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 728492.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUOX	NM_001032386.2 linkuse as main transcript	c.19G>A	p.Ala7Thr	missense_variant	3/5	ENST00000266971.8	NP_001027558.1	P51687A0A024RB79
SUOX	NM_000456.3 linkuse as main transcript	c.19G>A	p.Ala7Thr	missense_variant	4/6		NP_000447.2	P51687A0A024RB79
SUOX	NM_001032387.2 linkuse as main transcript	c.19G>A	p.Ala7Thr	missense_variant	2/4		NP_001027559.1	P51687A0A024RB79

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUOX	ENST00000266971.8 linkuse as main transcript	c.19G>A	p.Ala7Thr	missense_variant	3/5	2	NM_001032386.2	ENSP00000266971.3		P51687

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152180

Hom.:

Cov.:

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000998

AC:

AN:

250426

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135452

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000484

Gnomad NFE exome

AF:

0.000193

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000602

AC:

AN:

1460638

Hom.:

Cov.:

AF XY:

0.0000716

AC XY:

AN XY:

726680

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000766

Gnomad4 NFE exome

AF:

0.0000656

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000128

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000178

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 08, 2022

The c.19G>A (p.A7T) alteration is located in exon 4 (coding exon 1) of the SUOX gene. This alteration results from a G to A substitution at nucleotide position 19, causing the alanine (A) at amino acid position 7 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Sulfite oxidase deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 26, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.23

CADD

Benign

9.9

DANN

Benign

0.97

DEOGEN2

Benign

0.32

T;T;T;.;.;T;.;.;T

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.64

.;.;.;T;T;.;T;T;.

M_CAP

Benign

0.019

MetaRNN

Benign

0.055

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.55

MutationAssessor

Benign

1.7

L;L;L;.;.;L;.;.;L

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.51

N;N;N;D;N;N;N;D;N

REVEL

Benign

0.18

Sift

Benign

0.37

T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.29

T;T;T;T;T;T;D;D;T

Polyphen

0.0

B;B;B;B;.;B;.;.;B

Vest4

0.20

MVP

0.58

MPC

0.12

ClinPred

0.025

GERP RS

-2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.028

gMVP

0.37

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

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