Variant 1-180166566-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000367602.8(QSOX1):c.341A>G(p.Asn114Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,614,066 control chromosomes in the GnomAD database, including 135 homozygotes. 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 Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.016 ( 78 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 57 hom. )

Consequence

QSOX1
ENST00000367602.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.24

Variant links:

Genes affected

QSOX1 (HGNC:9756): (quiescin sulfhydryl oxidase 1) This gene encodes a protein that contains domains of thioredoxin and ERV1, members of two long-standing gene families. The gene expression is induced as fibroblasts begin to exit the proliferative cycle and enter quiescence, suggesting that this gene plays an important role in growth regulation. Two transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

QSOX1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032423139).

BP6

Variant 1-180166566-A-G is Benign according to our data. Variant chr1-180166566-A-G is described in ClinVar as [Benign]. Clinvar id is 780282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
QSOX1	NM_002826.5 linkuse as main transcript	c.341A>G	p.Asn114Ser	missense_variant	2/12	ENST00000367602.8	NP_002817.2
QSOX1	NM_001004128.3 linkuse as main transcript	c.341A>G	p.Asn114Ser	missense_variant	2/13		NP_001004128.1
QSOX1	XM_047426230.1 linkuse as main transcript	c.341A>G	p.Asn114Ser	missense_variant	2/13		XP_047282186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
QSOX1	ENST00000367602.8 linkuse as main transcript	c.341A>G	p.Asn114Ser	missense_variant	2/12	1	NM_002826.5	ENSP00000356574	P2	O00391-1
QSOX1	ENST00000367600.5 linkuse as main transcript	c.341A>G	p.Asn114Ser	missense_variant	2/13	1		ENSP00000356572	A2	O00391-2
QSOX1	ENST00000392029.6 linkuse as main transcript	c.341A>G	p.Asn114Ser	missense_variant, NMD_transcript_variant	2/8	5		ENSP00000375883

Frequencies

GnomAD3 genomes

AF:

0.0158

AC:

2402

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0545

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00694

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:

0.000147

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00422

AC:

1061

AN:

251300

Hom.:

AF XY:

0.00288

AC XY:

391

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.0570

Gnomad AMR exome

AF:

0.00307

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00178

AC:

2598

AN:

1461790

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

1094

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.0589

Gnomad4 AMR exome

AF:

0.00300

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000233

Gnomad4 OTH exome

AF:

0.00359

GnomAD4 genome

AF:

0.0158

AC:

2413

AN:

152276

Hom.:

Cov.:

AF XY:

0.0149

AC XY:

1108

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0546

Gnomad4 AMR

AF:

0.00693

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00295

Hom.:

Bravo

AF:

0.0185

ESP6500AA

AF:

0.0570

AC:

251

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00527

AC:

640

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

T;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.78

T;T

MetaRNN

Benign

0.0032

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

N;N

MutationTaster

Benign

0.96

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.046

Sift

Benign

0.23

T;T

Sift4G

Uncertain

0.043

D;T

Polyphen

0.10

B;P

Vest4

0.25

MVP

0.14

MPC

0.14

ClinPred

0.029

GERP RS

2.5

Varity_R

0.17

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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