rs1044032

chr15-45676237-T-C

Variant summary

Our verdict is Benign. Variant got -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. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SQOR	NM_021199.4	c.791T>C	p.Ile264Thr	missense_variant	6/10	ENST00000260324.12
SQOR	NM_001271213.2	c.791T>C	p.Ile264Thr	missense_variant	7/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SQOR	ENST00000260324.12	c.791T>C	p.Ile264Thr	missense_variant	6/10	1	NM_021199.4	P1
SQOR	ENST00000568606.5	c.791T>C	p.Ile264Thr	missense_variant	7/11	5		P1

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

GnomAD3 exomes AF: 0.245 AC: 61459 AN: 251202 Hom.: 8473 AF XY: 0.250 AC XY: 33947 AN XY: 135780

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 SAS exome AF: 0.371

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

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.228

Gnomad4 ASJ exome AF: 0.218

Gnomad4 EAS exome AF: 0.433

Gnomad4 SAS exome AF: 0.364

Gnomad4 FIN exome AF: 0.255

Gnomad4 NFE exome AF: 0.201

Gnomad4 OTH exome AF: 0.233

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

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.208

Alfa AF: 0.210 Hom.: 8977

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 v4.3

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
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.061
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.68	T;.;T
MetaRNN	Benign	0.0012	T;T;T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	0.000050	P;P
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.2	D;D;D
Sift	Benign	0.095	T;T;T
Sift4G	Benign	0.13	T;T;T
Polyphen		0.0060	.;B;B
Vest4		0.071, 0.075
MPC		0.084
ClinPred		0.049	T
GERP RS		4.6
Varity_R		0.38
gMVP		0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs1044032; hg19: chr15-45968435; COSMIC: COSV52940775; COSMIC: COSV52940775;