chr15-45661963-C-A

Variant names:

• chr15-45661963-C-A
• NM_021199.4:c.243C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021199.4(SQOR):​c.243C>A​(p.Phe81Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 1.02

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SQOR	NM_021199.4	c.243C>A	p.Phe81Leu	missense_variant	Exon 3 of 10	ENST00000260324.12	NP_067022.1
SQOR	NM_001271213.2	c.243C>A	p.Phe81Leu	missense_variant	Exon 4 of 11		NP_001258142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SQOR	ENST00000260324.12	c.243C>A	p.Phe81Leu	missense_variant	Exon 3 of 10	1	NM_021199.4	ENSP00000260324.7
ENSG00000260170	ENST00000564080.1	c.243C>A	p.Phe81Leu	missense_variant	Exon 3 of 6	3		ENSP00000455047.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.243C>A (p.F81L) alteration is located in exon 3 (coding exon 2) of the SQRDL gene. This alteration results from a C to A substitution at nucleotide position 243, causing the phenylalanine (F) at amino acid position 81 to be replaced by a leucine (L). 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	Pathogenic	0.93
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	.;T;.;T;.
Eigen	Benign	-0.11
Eigen_PC	Benign	0.089
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D;.;D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.45	T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-4.2	D;D;D;D;D
REVEL	Benign	0.16
Sift	Uncertain	0.0030	D;D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D;D
Polyphen		0.0060	.;B;.;B;.
Vest4		0.49
MutPred		0.61		Loss of catalytic residue at Q83 (P = 0.0993);Loss of catalytic residue at Q83 (P = 0.0993);Loss of catalytic residue at Q83 (P = 0.0993);Loss of catalytic residue at Q83 (P = 0.0993);Loss of catalytic residue at Q83 (P = 0.0993);
MVP		0.30
MPC		0.24
ClinPred		0.97	D
GERP RS		4.4
Varity_R		0.88
gMVP		0.77

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: chr15-45954161;