12-56001905-G-C

Variant names:

• chr12-56001905-G-C
• rs7963590
• ENST00000394109.7:c.-317G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000394109.7(SUOX):​c.-317G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000815 in 1,103,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: SUOX ENST00000394109.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425
• Publications: 6 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, G2P

ACMG classification

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 (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUOX	NM_001032386.2	c.-10-307G>C		intron_variant	Intron 2 of 4	ENST00000266971.8	NP_001027558.1
SUOX	NM_000456.3	c.-10-307G>C		intron_variant	Intron 3 of 5		NP_000447.2
SUOX	NM_001032387.2	c.-10-307G>C		intron_variant	Intron 1 of 3		NP_001027559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUOX	ENST00000266971.8	c.-10-307G>C		intron_variant	Intron 2 of 4	2	NM_001032386.2	ENSP00000266971.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000815 AC: 9 AN: 1103868 Hom.: 0 Cov.: 30 AF XY: 0.0000114 AC XY: 6 AN XY: 528544

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 23800

American (AMR) AF: 0.00 AC: 0 AN: 14120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12970

East Asian (EAS) AF: 0.00 AC: 0 AN: 18720

South Asian (SAS) AF: 0.00 AC: 0 AN: 55680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2724

European-Non Finnish (NFE) AF: 0.00000870 AC: 8 AN: 919544

Other (OTH) AF: 0.0000237 AC: 1 AN: 42230

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000434654), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 89

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.6
DANN	Benign	0.57
PhyloP100		0.42
PromoterAI		-0.028	Neutral

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

Other links and lift over

dbSNP: rs7963590; hg19: chr12-56395689;