Genetic Variant SQOR:p.Val318Met (chr15-45682565-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_021199.4(SQOR):c.952G>A(p.Val318Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 1,614,220 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 6 hom. )

Consequence

SQOR
NM_021199.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.78

Publications

10 publications found

Variant links:

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

SQOR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07827324).

BP6

Variant 15-45682565-G-A is Benign according to our data. Variant chr15-45682565-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3034734.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

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.952G>A	p.Val318Met	missense	Exon 7 of 10	NP_067022.1	Q9Y6N5
	SQOR	NM_001271213.2		c.952G>A	p.Val318Met	missense	Exon 8 of 11	NP_001258142.1	Q9Y6N5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SQOR	ENST00000260324.12	TSL:1 MANE Select	c.952G>A	p.Val318Met	missense	Exon 7 of 10	ENSP00000260324.7	Q9Y6N5
SQOR	ENST00000568606.5	TSL:5	c.952G>A	p.Val318Met	missense	Exon 8 of 11	ENSP00000456019.1	Q9Y6N5
SQOR	ENST00000888093.1		c.952G>A	p.Val318Met	missense	Exon 7 of 10	ENSP00000558152.1

Frequencies

GnomAD3 genomes

AF:

0.00162

AC:

247

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00275

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00190

AC:

478

AN:

251416

AF XY:

0.00202

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00298

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000554

Gnomad NFE exome

AF:

0.00315

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00265

AC:

3876

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00262

AC XY:

1902

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.000657

AC:

AN:

33476

American (AMR)

AF:

0.00119

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00310

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000336

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000618

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00468

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00315

AC:

3501

AN:

1112008

Other (OTH)

AF:

0.00215

AC:

130

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

208

416

625

833

1041

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

130

260

390

520

650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00162

AC:

247

AN:

152336

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

114

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.000674

AC:

AN:

41572

American (AMR)

AF:

0.000654

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000471

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00275

AC:

187

AN:

68036

Other (OTH)

AF:

0.00379

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00286

Hom.:

Bravo

AF:

0.00175

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00303

AC:

ExAC

AF:

0.00191

AC:

232

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00469

EpiControl

AF:

0.00427

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

SQOR-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.70

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.065

MetaRNN

Benign

0.078

MetaSVM

Uncertain

0.49

PhyloP100

2.8

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.63

MVP

0.81

MPC

0.35

ClinPred

0.24

GERP RS

5.0

PromoterAI

-0.027

Neutral

(source)

Varity_R

0.79

gMVP

0.81

Mutation Taster

=39/61

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over