15-45676237-T-C

Variant names:

• chr15-45676237-T-C
• rs1044032
• NM_021199.4:c.791T>C

Variant summary

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

The NM_021199.4(SQOR):​c.791T>C​(p.Ile264Thr) variant causes a missense change. The variant allele was found at a frequency of 0.217 in 1,613,820 control chromosomes in the GnomAD database, including 41,217 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3295 hom., cov: 32)
  • Exomes 𝑓: 0.22 (37922 hom.)
• Consequence: SQOR NM_021199.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.23
• Publications: 43 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, MODERATE Submitted by: PanelApp Australia, 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 (MetaRNN=0.001188308).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 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.791T>C	p.Ile264Thr	missense	Exon 6 of 10	NP_067022.1	Q9Y6N5
	SQOR	NM_001271213.2		c.791T>C	p.Ile264Thr	missense	Exon 7 of 11	NP_001258142.1	Q9Y6N5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SQOR	ENST00000260324.12	TSL:1 MANE Select	c.791T>C	p.Ile264Thr	missense	Exon 6 of 10	ENSP00000260324.7	Q9Y6N5
	ENSG00000260170	ENST00000564080.1	TSL:3	c.791T>C	p.Ile264Thr	missense	Exon 6 of 6	ENSP00000455047.1	H3BNX3
	SQOR	ENST00000568606.5	TSL:5	c.791T>C	p.Ile264Thr	missense	Exon 7 of 11	ENSP00000456019.1	Q9Y6N5

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29957 AN: 151932 Hom.: 3288 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.202

GnomAD2 exomes AF: 0.245 AC: 61459 AN: 251202 AF XY: 0.250

Gnomad AFR exome AF: 0.113

Gnomad AMR exome AF: 0.231

Gnomad ASJ exome AF: 0.220

Gnomad EAS exome AF: 0.443

Gnomad FIN exome AF: 0.256

Gnomad NFE exome AF: 0.202

Gnomad OTH exome AF: 0.235

GnomAD4 exome AF: 0.219 AC: 320272 AN: 1461770 Hom.: 37922 Cov.: 38 AF XY: 0.223 AC XY: 162432 AN XY: 727184

African (AFR) AF: 0.110 AC: 3672 AN: 33480

American (AMR) AF: 0.228 AC: 10174 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 5695 AN: 26136

East Asian (EAS) AF: 0.433 AC: 17180 AN: 39694

South Asian (SAS) AF: 0.364 AC: 31390 AN: 86254

European-Finnish (FIN) AF: 0.255 AC: 13635 AN: 53406

Middle Eastern (MID) AF: 0.227 AC: 1310 AN: 5764

European-Non Finnish (NFE) AF: 0.201 AC: 223152 AN: 1111932

Other (OTH) AF: 0.233 AC: 14064 AN: 60388

GnomAD4 genome AF: 0.197 AC: 29970 AN: 152050 Hom.: 3295 Cov.: 32 AF XY: 0.202 AC XY: 15036 AN XY: 74296

African (AFR) AF: 0.112 AC: 4658 AN: 41498

American (AMR) AF: 0.220 AC: 3366 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 716 AN: 3468

East Asian (EAS) AF: 0.426 AC: 2197 AN: 5160

South Asian (SAS) AF: 0.363 AC: 1748 AN: 4820

European-Finnish (FIN) AF: 0.254 AC: 2681 AN: 10546

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13864 AN: 67976

Other (OTH) AF: 0.208 AC: 437 AN: 2098

Alfa AF: 0.206 Hom.: 11894

Bravo AF: 0.192

TwinsUK AF: 0.196 AC: 726

ALSPAC AF: 0.196 AC: 756

ESP6500AA AF: 0.111 AC: 490

ESP6500EA AF: 0.204 AC: 1756

ExAC AF: 0.243 AC: 29486

Asia WGS AF: 0.389 AC: 1353 AN: 3478

EpiCase AF: 0.212

EpiControl AF: 0.205

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.40	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.061
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-0.95	T
PhyloP100		6.2
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.14
Sift	Benign	0.095	T
Sift4G	Benign	0.13	T
Polyphen		0.0060	B
Vest4		0.071
MPC		0.084
ClinPred		0.049	T
GERP RS		4.6
Varity_R		0.38
gMVP		0.61
Mutation Taster		=92/8	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: rs1044032; hg19: chr15-45968435; COSMIC: COSV52940775; COSMIC: COSV52940775;