Variant 15-45673631-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.484G>A(p.Ala162Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,770 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: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

SQOR
NM_021199.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.87

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:

Genome browser will be placed here

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=0.1277287).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SQOR	NM_021199.4 linkuse as main transcript	c.484G>A	p.Ala162Thr	missense_variant	5/10	ENST00000260324.12	NP_067022.1	Q9Y6N5A0A024R5X2
SQOR	NM_001271213.2 linkuse as main transcript	c.484G>A	p.Ala162Thr	missense_variant	6/11		NP_001258142.1	Q9Y6N5A0A024R5X2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SQOR	ENST00000260324.12 linkuse as main transcript	c.484G>A	p.Ala162Thr	missense_variant	5/10	1	NM_021199.4	ENSP00000260324.7	Q9Y6N5
ENSG00000260170	ENST00000564080.1 linkuse as main transcript	c.484G>A	p.Ala162Thr	missense_variant	5/6	3		ENSP00000455047.1	H3BNX3
SQOR	ENST00000568606.5 linkuse as main transcript	c.484G>A	p.Ala162Thr	missense_variant	6/11	5		ENSP00000456019.1	Q9Y6N5
SQOR	ENST00000566934.1 linkuse as main transcript	c.325G>A	p.Ala109Thr	missense_variant	4/4	2		ENSP00000454520.1	H3BMS6

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251110

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135686

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461602

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000164

Hom.:

Bravo

AF:

0.000117

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

Jun 19, 2024

The c.484G>A (p.A162T) alteration is located in exon 5 (coding exon 4) of the SQRDL gene. This alteration results from a G to A substitution at nucleotide position 484, causing the alanine (A) at amino acid position 162 to be replaced by a threonine (T). 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

0.076

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

.;T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

0.0067

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.87

D;.;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.63

N;N;N

REVEL

Benign

0.099

Sift

Benign

0.11

T;D;D

Sift4G

Benign

0.32

T;T;T

Polyphen

0.046

.;B;B

Vest4

0.31, 0.30

MVP

0.24

MPC

0.071

ClinPred

0.24

GERP RS

2.3

Varity_R

0.12

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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