chr12-56004039-GG-AA

Variant names:

• chr12-56004039-GG-AA
• NM_001032386.2:c.650_651delGGinsAA
• SUOX p.Arg217Gln

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PS1_Very_Strong PM5 PP3

The NM_001032386.2(SUOX):​c.650_651delGGinsAA​(p.Arg217Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely pathogenic in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R217W) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SUOX NM_001032386.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.90
• Publications: 0 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, Ambry Genetics, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PS1: Transcript NM_001032386.2 (SUOX) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr12-56004038-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 985679.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.650_651delGGinsAA	p.Arg217Gln	missense	N/A	NP_001027558.1	P51687
	SUOX	NM_000456.3		c.650_651delGGinsAA	p.Arg217Gln	missense	N/A	NP_000447.2	P51687
	SUOX	NM_001032387.2		c.650_651delGGinsAA	p.Arg217Gln	missense	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.650_651delGGinsAA	p.Arg217Gln	missense	N/A	ENSP00000266971.3	P51687
	SUOX	ENST00000356124.8	TSL:1	c.650_651delGGinsAA	p.Arg217Gln	missense	N/A	ENSP00000348440.4	P51687
	SUOX	ENST00000394109.7	TSL:1	c.650_651delGGinsAA	p.Arg217Gln	missense	N/A	ENSP00000377668.3	P51687

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-56397823;