Variant 15-45659006-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021199.4(SQOR):c.83G>A(p.Gly28Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000759 in 1,450,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

SQOR
NM_021199.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.07

Variant links:

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 links:

ENSG00000260170 (HGNC:):

ENSG00000260170 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10734981).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SQOR	NM_021199.4 linkuse as main transcript	c.83G>A	p.Gly28Asp	missense_variant	2/10	ENST00000260324.12	NP_067022.1	Q9Y6N5A0A024R5X2
SQOR	NM_001271213.2 linkuse as main transcript	c.83G>A	p.Gly28Asp	missense_variant	3/11		NP_001258142.1	Q9Y6N5A0A024R5X2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SQOR	ENST00000260324.12 linkuse as main transcript	c.83G>A	p.Gly28Asp	missense_variant	2/10	1	NM_021199.4	ENSP00000260324.7		Q9Y6N5
ENSG00000260170	ENST00000564080.1 linkuse as main transcript	c.83G>A	p.Gly28Asp	missense_variant	2/6	3		ENSP00000455047.1		H3BNX3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000874

AC:

AN:

228908

Hom.:

AF XY:

0.0000161

AC XY:

AN XY:

123952

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000194

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000759

AC:

AN:

1450108

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

719966

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000994

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 02, 2023

The c.83G>A (p.G28D) alteration is located in exon 2 (coding exon 1) of the SQRDL gene. This alteration results from a G to A substitution at nucleotide position 83, causing the glycine (G) at amino acid position 28 to be replaced by an aspartic acid (D). 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

Benign

0.13

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.13

.;T;.;.;.;T;.

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.54

T;.;T;T;T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.11

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.66

N;N;N;D;N;N;N

REVEL

Benign

0.096

Sift

Uncertain

0.017

D;T;D;D;D;T;D

Sift4G

Benign

0.16

T;T;T;T;T;T;T

Polyphen

0.13

.;B;.;.;.;B;.

Vest4

0.29, 0.29

MutPred

0.47

Gain of solvent accessibility (P = 0.1045);Gain of solvent accessibility (P = 0.1045);Gain of solvent accessibility (P = 0.1045);Gain of solvent accessibility (P = 0.1045);Gain of solvent accessibility (P = 0.1045);Gain of solvent accessibility (P = 0.1045);Gain of solvent accessibility (P = 0.1045);

MVP

0.18

MPC

0.078

ClinPred

0.065

GERP RS

2.5

Varity_R

0.060

gMVP

0.65

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over