NM_001032386.2:c.19G>C

Variant names:

• chr12-56002240-G-C
• rs375363943
• NM_001032386.2:c.19G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001032386.2(SUOX):​c.19G>C​(p.Ala7Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SUOX NM_001032386.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08448371).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUOX	NM_001032386.2	c.19G>C	p.Ala7Pro	missense_variant	Exon 3 of 5	ENST00000266971.8	NP_001027558.1
SUOX	NM_000456.3	c.19G>C	p.Ala7Pro	missense_variant	Exon 4 of 6		NP_000447.2
SUOX	NM_001032387.2	c.19G>C	p.Ala7Pro	missense_variant	Exon 2 of 4		NP_001027559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUOX	ENST00000266971.8	c.19G>C	p.Ala7Pro	missense_variant	Exon 3 of 5	2	NM_001032386.2	ENSP00000266971.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250426 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135452

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.37	T;T;T;.;.;T;.;.;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.60	.;.;.;T;T;.;T;T;.
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.084	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.3	L;L;L;.;.;L;.;.;L
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.92	N;N;N;D;N;N;N;D;N
REVEL	Uncertain	0.31
Sift	Benign	0.23	T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.16	T;T;T;D;D;T;D;D;T
Polyphen		0.0	B;B;B;B;.;B;.;.;B
Vest4		0.30
MutPred		0.38		Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);
MVP		0.60
MPC		0.17
ClinPred		0.034	T
GERP RS		-2.2
Varity_R		0.097
gMVP		0.52

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

Other links and lift over

dbSNP: rs375363943; hg19: chr12-56396024;