15-45668699-C-T

Variant names:

• chr15-45668699-C-T
• rs11637483
• NM_021199.4:c.406-1229C>T

Variant summary

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

The NM_021199.4(SQOR):​c.406-1229C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0776 in 152,220 control chromosomes in the GnomAD database, including 518 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 0.078 (518 hom., cov: 32)
• Consequence: SQOR NM_021199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139
• Publications: 5 publications found

Genes affected

SQOR (HGNC:20390): (sulfide quinone oxidoreductase) The protein encoded by this gene may function in mitochondria to catalyze the conversion of sulfide to persulfides, thereby decreasing toxic concencrations of sulfide. Alternative splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2012]

SQOR Gene-Disease associations (from GenCC):

• sulfide quinone oxidoreductase deficiency

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ENSG00000260170 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0992 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021199.4. 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
	SQOR	NM_021199.4	MANE Select	c.406-1229C>T		intron	N/A	NP_067022.1
	SQOR	NM_001271213.2		c.406-1229C>T		intron	N/A	NP_001258142.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SQOR	ENST00000260324.12	TSL:1 MANE Select	c.406-1229C>T		intron	N/A	ENSP00000260324.7
	ENSG00000260170	ENST00000564080.1	TSL:3	c.406-1229C>T		intron	N/A	ENSP00000455047.1
	SQOR	ENST00000568606.5	TSL:5	c.406-1229C>T		intron	N/A	ENSP00000456019.1

Frequencies

GnomAD3 genomes AF: 0.0776 AC: 11801 AN: 152102 Hom.: 518 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.0461

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0908

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0686

Gnomad OTH AF: 0.0718

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

GnomAD4 genome AF: 0.0776 AC: 11812 AN: 152220 Hom.: 518 Cov.: 32 AF XY: 0.0780 AC XY: 5810 AN XY: 74442

African (AFR) AF: 0.102 AC: 4225 AN: 41530

American (AMR) AF: 0.0460 AC: 703 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 431 AN: 3470

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5192

South Asian (SAS) AF: 0.101 AC: 487 AN: 4816

European-Finnish (FIN) AF: 0.0908 AC: 963 AN: 10600

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0686 AC: 4665 AN: 68008

Other (OTH) AF: 0.0705 AC: 149 AN: 2112

Alfa AF: 0.0693 Hom.: 797

Bravo AF: 0.0734

Asia WGS AF: 0.0420 AC: 147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.51
PhyloP100		0.14
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: rs11637483; hg19: chr15-45960897;