ENST00000394109.7:c.-628G>A

Variant names:

• chr12-56001594-G-A
• rs7297662
• ENST00000394109.7:c.-628G>A

Variant summary

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

The ENST00000394109.7(SUOX):​c.-628G>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 0.46 in 162,016 control chromosomes in the GnomAD database, including 17,609 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 0.46 (16296 hom., cov: 31)
  • Exomes 𝑓: 0.49 (1313 hom.)
• Consequence: SUOX ENST00000394109.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197
• Publications: 12 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000394109.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUOX	NM_001032386.2	MANE Select	c.-10-618G>A		intron	N/A	NP_001027558.1
	SUOX	NM_000456.3		c.-10-618G>A		intron	N/A	NP_000447.2
	SUOX	NM_001032387.2		c.-10-618G>A		intron	N/A	NP_001027559.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUOX	ENST00000394109.7	TSL:1	c.-628G>A		5_prime_UTR	Exon 1 of 3	ENSP00000377668.3
	SUOX	ENST00000266971.8	TSL:2 MANE Select	c.-10-618G>A		intron	N/A	ENSP00000266971.3
	SUOX	ENST00000356124.8	TSL:1	c.-10-618G>A		intron	N/A	ENSP00000348440.4

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69528 AN: 151772 Hom.: 16275 Cov.: 31

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.492

GnomAD4 exome AF: 0.488 AC: 4943 AN: 10126 Hom.: 1313 Cov.: 0 AF XY: 0.481 AC XY: 2452 AN XY: 5102

African (AFR) AF: 0.379 AC: 22 AN: 58

American (AMR) AF: 0.657 AC: 1384 AN: 2106

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 27 AN: 58

East Asian (EAS) AF: 0.383 AC: 154 AN: 402

South Asian (SAS) AF: 0.373 AC: 410 AN: 1098

European-Finnish (FIN) AF: 0.506 AC: 87 AN: 172

Middle Eastern (MID) AF: 0.300 AC: 3 AN: 10

European-Non Finnish (NFE) AF: 0.459 AC: 2654 AN: 5778

Other (OTH) AF: 0.455 AC: 202 AN: 444

GnomAD4 genome AF: 0.458 AC: 69574 AN: 151890 Hom.: 16296 Cov.: 31 AF XY: 0.465 AC XY: 34498 AN XY: 74238

African (AFR) AF: 0.383 AC: 15857 AN: 41404

American (AMR) AF: 0.613 AC: 9360 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1671 AN: 3472

East Asian (EAS) AF: 0.410 AC: 2109 AN: 5148

South Asian (SAS) AF: 0.385 AC: 1853 AN: 4818

European-Finnish (FIN) AF: 0.562 AC: 5926 AN: 10536

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31205 AN: 67930

Other (OTH) AF: 0.493 AC: 1040 AN: 2108

Alfa AF: 0.471 Hom.: 28635

Bravo AF: 0.468

Asia WGS AF: 0.387 AC: 1348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.76
PhyloP100		0.20
PromoterAI		-0.027	Neutral
Mutation Taster		=299/1	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: rs7297662; hg19: chr12-56395378;