NM_021199.4:c.952G>T

Variant names:

• chr15-45682565-G-T
• rs140459079
• NM_021199.4:c.952G>T

Variant summary

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

The NM_021199.4(SQOR):​c.952G>T​(p.Val318Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. V318M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SQOR NM_021199.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.78
• Publications: 0 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

ACMG classification

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.952G>T	p.Val318Leu	missense	Exon 7 of 10	NP_067022.1	Q9Y6N5
	SQOR	NM_001271213.2		c.952G>T	p.Val318Leu	missense	Exon 8 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.952G>T	p.Val318Leu	missense	Exon 7 of 10	ENSP00000260324.7	Q9Y6N5
	SQOR	ENST00000568606.5	TSL:5	c.952G>T	p.Val318Leu	missense	Exon 8 of 11	ENSP00000456019.1	Q9Y6N5
	SQOR	ENST00000888093.1		c.952G>T	p.Val318Leu	missense	Exon 7 of 10	ENSP00000558152.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Uncertain	-0.073	T
PhyloP100		2.8
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.013	D
Polyphen		0.73	P
Vest4		0.37
MutPred		0.77		Gain of ubiquitination at K320 (P = 0.1204)
MVP		0.72
MPC		0.073
ClinPred		0.96	D
GERP RS		5.0
PromoterAI		-0.028	Neutral
Varity_R		0.76
gMVP		0.78

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: rs140459079; hg19: chr15-45974763;