Genetic Variant NM_021199.4:c.181C>A (chr15-45659104-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021199.4(SQOR):c.181C>A(p.Arg61Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R61H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SQOR
NM_021199.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.32

Publications

1 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:

ENSG00000260170 (HGNC:):

ENSG00000260170 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.181C>A	p.Arg61Ser	missense	Exon 2 of 10	NP_067022.1	Q9Y6N5
	SQOR	NM_001271213.2		c.181C>A	p.Arg61Ser	missense	Exon 3 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.181C>A	p.Arg61Ser	missense	Exon 2 of 10	ENSP00000260324.7	Q9Y6N5
ENSG00000260170	ENST00000564080.1	TSL:3	c.181C>A	p.Arg61Ser	missense	Exon 2 of 6	ENSP00000455047.1	H3BNX3
SQOR	ENST00000568606.5	TSL:5	c.181C>A	p.Arg61Ser	missense	Exon 3 of 11	ENSP00000456019.1	Q9Y6N5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000473

AC:

AN:

211278

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000105

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1429112

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706166

African (AFR)

AF:

0.00

AC:

AN:

33146

American (AMR)

AF:

0.00

AC:

AN:

39538

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25248

East Asian (EAS)

AF:

0.00

AC:

AN:

38656

South Asian (SAS)

AF:

0.00

AC:

AN:

82038

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51992

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5054

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1094356

Other (OTH)

AF:

0.00

AC:

AN:

59084

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.10

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Benign

0.094

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.66

MetaSVM

Benign

-1.0

PhyloP100

4.3

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.23

Sift

Benign

0.062

Sift4G

Uncertain

0.050

Polyphen

0.32

Vest4

0.85

MutPred

0.63

Loss of MoRF binding (P = 0.011)

MVP

0.27

MPC

0.41

ClinPred

0.97

GERP RS

5.5

PromoterAI

0.014

Neutral

(source)

Varity_R

0.93

gMVP

0.90

Mutation Taster

=9/91

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over