15-45673714-T-G

Variant names:

• chr15-45673714-T-G
• NM_021199.4:c.567T>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021199.4(SQOR):​c.567T>G​(p.Asn189Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SQOR NM_021199.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.428

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]

ENSG00000260170 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39837274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SQOR	NM_021199.4	c.567T>G	p.Asn189Lys	missense_variant	Exon 5 of 10	ENST00000260324.12	NP_067022.1
SQOR	NM_001271213.2	c.567T>G	p.Asn189Lys	missense_variant	Exon 6 of 11		NP_001258142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SQOR	ENST00000260324.12	c.567T>G	p.Asn189Lys	missense_variant	Exon 5 of 10	1	NM_021199.4	ENSP00000260324.7
ENSG00000260170	ENST00000564080.1	c.567T>G	p.Asn189Lys	missense_variant	Exon 5 of 6	3		ENSP00000455047.1
SQOR	ENST00000568606.5	c.567T>G	p.Asn189Lys	missense_variant	Exon 6 of 11	5		ENSP00000456019.1
SQOR	ENST00000566934.1	c.408T>G	p.Asn136Lys	missense_variant	Exon 4 of 4	2		ENSP00000454520.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.567T>G (p.N189K) alteration is located in exon 5 (coding exon 4) of the SQRDL gene. This alteration results from a T to G substitution at nucleotide position 567, causing the asparagine (N) at amino acid position 189 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	.;T;T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.96	D;.;D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-5.5	D;D;D
REVEL	Benign	0.11
Sift	Uncertain	0.028	D;D;D
Sift4G	Uncertain	0.043	D;D;D
Polyphen		0.24	.;B;B
Vest4		0.89, 0.89
MutPred		0.51		Loss of catalytic residue at N189 (P = 0.0018);Loss of catalytic residue at N189 (P = 0.0018);Loss of catalytic residue at N189 (P = 0.0018);
MVP		0.20
MPC		0.40
ClinPred		0.99	D
GERP RS		0.70
Varity_R		0.76
gMVP		0.91

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-45965912;