15-45659104-C-G

Variant names:

• chr15-45659104-C-G
• rs376077055
• NM_021199.4:c.181C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_021199.4(SQOR):​c.181C>G​(p.Arg61Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000007 in 1,429,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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: 7.0e-7 (0 hom.)
• Consequence: SQOR NM_021199.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.32
• Publications: 1 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.86

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>G	p.Arg61Gly	missense	Exon 2 of 10	NP_067022.1	Q9Y6N5
	SQOR	NM_001271213.2		c.181C>G	p.Arg61Gly	missense	Exon 3 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.181C>G	p.Arg61Gly	missense	Exon 2 of 10	ENSP00000260324.7	Q9Y6N5
	ENSG00000260170	ENST00000564080.1	TSL:3	c.181C>G	p.Arg61Gly	missense	Exon 2 of 6	ENSP00000455047.1	H3BNX3
	SQOR	ENST00000568606.5	TSL:5	c.181C>G	p.Arg61Gly	missense	Exon 3 of 11	ENSP00000456019.1	Q9Y6N5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000473 AC: 1 AN: 211278 AF XY: 0.00

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 AF: 7.00e-7 AC: 1 AN: 1429112 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 706166

African (AFR) AF: 0.00 AC: 0 AN: 33146

American (AMR) AF: 0.00 AC: 0 AN: 39538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25248

East Asian (EAS) AF: 0.00 AC: 0 AN: 38656

South Asian (SAS) AF: 0.00 AC: 0 AN: 82038

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51992

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5054

European-Non Finnish (NFE) AF: 9.14e-7 AC: 1 AN: 1094356

Other (OTH) AF: 0.00 AC: 0 AN: 59084

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.38	T
PhyloP100		4.3
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.83	P
Vest4		0.89
MutPred		0.67		Loss of MoRF binding (P = 0.0053)
MVP		0.64
MPC		0.43
ClinPred		0.98	D
GERP RS		5.5
PromoterAI		0.051	Neutral
Varity_R		0.93
gMVP		0.91
Mutation Taster		=9/91	disease causing

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: rs376077055; hg19: chr15-45951302;