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

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 3034734.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SQOR	NM_021199.4 link	c.952G>A	p.Val318Met	missense_variant	Exon 7 of 10	ENST00000260324.12	NP_067022.1	Q9Y6N5A0A024R5X2
SQOR	NM_001271213.2 link	c.952G>A	p.Val318Met	missense_variant	Exon 8 of 11		NP_001258142.1	Q9Y6N5A0A024R5X2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SQOR	ENST00000260324.12 link	c.952G>A	p.Val318Met	missense_variant	Exon 7 of 10	1	NM_021199.4	ENSP00000260324.7	Q9Y6N5
SQOR	ENST00000568606.5 link	c.952G>A	p.Val318Met	missense_variant	Exon 8 of 11	5		ENSP00000456019.1	Q9Y6N5
SQOR	ENST00000565997.1 link	c.25G>A	p.Val9Met	missense_variant	Exon 1 of 3	2		ENSP00000454953.1	H3BNP9

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

GnomAD3 exomes

AF:

0.00190

AC:

478

AN:

251416

Hom.:

AF XY:

0.00202

AC XY:

274

AN XY:

135888

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 SAS exome

AF:

0.000294

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

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00119

Gnomad4 ASJ exome

AF:

0.00310

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000336

Gnomad4 FIN exome

AF:

0.000618

Gnomad4 NFE exome

AF:

0.00315

Gnomad4 OTH exome

AF:

0.00215

GnomAD4 genome

AF:

0.00162

AC:

247

AN:

152336

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

114

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00275

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00326

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SQOR-related disorder

Benign:1

May 24, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.70

D;D

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

.;D

M_CAP

Benign

0.065

MetaRNN

Benign

0.078

T;T

MetaSVM

Uncertain

0.49

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.9

D;D

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;D

Vest4

0.63

MVP

0.81

MPC

0.35

ClinPred

0.24

GERP RS

5.0

Varity_R

0.79

gMVP

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over