ENST00000394109.7:c.-317G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000394109.7(SUOX):​c.-317G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 1,255,350 control chromosomes in the GnomAD database, including 3,838 homozygotes. 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: 𝑓 0.068 (400 hom., cov: 31)
  • Exomes 𝑓: 0.077 (3438 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUOX	NM_001032386.2	c.-10-307G>A		intron_variant	Intron 2 of 4	ENST00000266971.8	NP_001027558.1
SUOX	NM_000456.3	c.-10-307G>A		intron_variant	Intron 3 of 5		NP_000447.2
SUOX	NM_001032387.2	c.-10-307G>A		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>A		intron_variant	Intron 2 of 4	2	NM_001032386.2	ENSP00000266971.3

Frequencies

GnomAD3 genomes AF: 0.0685 AC: 10416 AN: 152066 Hom.: 400 Cov.: 31

Gnomad AFR AF: 0.0626

Gnomad AMI AF: 0.0879

Gnomad AMR AF: 0.0453

Gnomad ASJ AF: 0.0740

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0537

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0784

Gnomad OTH AF: 0.0569

GnomAD4 exome AF: 0.0768 AC: 84750 AN: 1103166 Hom.: 3438 Cov.: 30 AF XY: 0.0761 AC XY: 40182 AN XY: 528212

African (AFR) AF: 0.0645 AC: 1534 AN: 23784

American (AMR) AF: 0.0402 AC: 567 AN: 14118

Ashkenazi Jewish (ASJ) AF: 0.0701 AC: 908 AN: 12952

East Asian (EAS) AF: 0.000267 AC: 5 AN: 18720

South Asian (SAS) AF: 0.0538 AC: 2995 AN: 55646

European-Finnish (FIN) AF: 0.0943 AC: 1327 AN: 14072

Middle Eastern (MID) AF: 0.0767 AC: 209 AN: 2724

European-Non Finnish (NFE) AF: 0.0807 AC: 74200 AN: 918940

Other (OTH) AF: 0.0712 AC: 3005 AN: 42210

GnomAD4 genome AF: 0.0685 AC: 10418 AN: 152184 Hom.: 400 Cov.: 31 AF XY: 0.0691 AC XY: 5140 AN XY: 74408

African (AFR) AF: 0.0625 AC: 2593 AN: 41504

American (AMR) AF: 0.0452 AC: 691 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0740 AC: 257 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.0535 AC: 258 AN: 4818

European-Finnish (FIN) AF: 0.100 AC: 1059 AN: 10588

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0785 AC: 5336 AN: 68014

Other (OTH) AF: 0.0559 AC: 118 AN: 2112

Alfa AF: 0.0500 Hom.: 89

Bravo AF: 0.0635

Asia WGS AF: 0.0220 AC: 75 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.2
DANN	Benign	0.62
PhyloP100		0.42
PromoterAI		-0.050	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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;