chr15-45662024-C-T

Variant names:

• chr15-45662024-C-T
• rs781675712
• NM_021199.4:c.304C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021199.4(SQOR):​c.304C>T​(p.Pro102Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SQOR NM_021199.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.588
• 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

ENSG00000260170 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08189249).

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.304C>T	p.Pro102Ser	missense	Exon 3 of 10	NP_067022.1	Q9Y6N5
	SQOR	NM_001271213.2		c.304C>T	p.Pro102Ser	missense	Exon 4 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.304C>T	p.Pro102Ser	missense	Exon 3 of 10	ENSP00000260324.7	Q9Y6N5
	ENSG00000260170	ENST00000564080.1	TSL:3	c.304C>T	p.Pro102Ser	missense	Exon 3 of 6	ENSP00000455047.1	H3BNX3
	SQOR	ENST00000568606.5	TSL:5	c.304C>T	p.Pro102Ser	missense	Exon 4 of 11	ENSP00000456019.1	Q9Y6N5

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251462 AF XY: 0.00000736

Gnomad AFR exome AF: 0.000123

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461884 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727246

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152212 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74364

African (AFR) AF: 0.0000724 AC: 3 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	10
DANN	Benign	0.40
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.59
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.054
Sift	Benign	0.46	T
Sift4G	Benign	0.68	T
Polyphen		0.0010	B
Vest4		0.22
MutPred		0.48		Gain of catalytic residue at P102 (P = 0.0203)
MVP		0.17
MPC		0.063
ClinPred		0.11	T
GERP RS		1.5
Varity_R		0.20
gMVP		0.69
Mutation Taster		=64/36	polymorphism

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: rs781675712; hg19: chr15-45954222;