chr15-45642671-C-A

Variant names:

• chr15-45642671-C-A
• rs607541
• NM_021199.4:c.-18+7563C>A

Variant summary

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

The NM_021199.4(SQOR):​c.-18+7563C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 151,984 control chromosomes in the GnomAD database, including 6,635 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 0.26 (6635 hom., cov: 32)
• Consequence: SQOR NM_021199.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.74
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SQOR	NM_021199.4	c.-18+7563C>A		intron_variant	Intron 1 of 9	ENST00000260324.12	NP_067022.1
SQOR	NM_001271213.2	c.-18+10652C>A		intron_variant	Intron 2 of 10		NP_001258142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SQOR	ENST00000260324.12	c.-18+7563C>A		intron_variant	Intron 1 of 9	1	NM_021199.4	ENSP00000260324.7
ENSG00000260170	ENST00000564080.1	c.-17-16236C>A		intron_variant	Intron 1 of 5	3		ENSP00000455047.1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39874 AN: 151864 Hom.: 6606 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.263 AC: 39948 AN: 151984 Hom.: 6635 Cov.: 32 AF XY: 0.265 AC XY: 19697 AN XY: 74306

African (AFR) AF: 0.361 AC: 14936 AN: 41420

American (AMR) AF: 0.392 AC: 5979 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1013 AN: 3458

East Asian (EAS) AF: 0.643 AC: 3319 AN: 5164

South Asian (SAS) AF: 0.264 AC: 1273 AN: 4820

European-Finnish (FIN) AF: 0.156 AC: 1653 AN: 10596

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11146 AN: 67950

Other (OTH) AF: 0.264 AC: 557 AN: 2112

Alfa AF: 0.211 Hom.: 11071

Bravo AF: 0.292

Asia WGS AF: 0.451 AC: 1567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0060
DANN	Benign	0.68
PhyloP100		-3.7
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: rs607541; hg19: chr15-45934869;