Variant 1-180178859-A-C 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_002826.5(QSOX1):c.581A>C(p.Lys194Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,613,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

QSOX1
NM_002826.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.81

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 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=0.18339637).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QSOX1	NM_002826.5 linkuse as main transcript	c.581A>C	p.Lys194Thr	missense_variant	5/12	ENST00000367602.8	NP_002817.2	O00391-1Q13876
QSOX1	NM_001004128.3 linkuse as main transcript	c.581A>C	p.Lys194Thr	missense_variant	5/13		NP_001004128.1	O00391-2A0A140VKE5Q13876
QSOX1	XM_047426230.1 linkuse as main transcript	c.581A>C	p.Lys194Thr	missense_variant	5/13		XP_047282186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
QSOX1	ENST00000367602.8 linkuse as main transcript	c.581A>C	p.Lys194Thr	missense_variant	5/12	1	NM_002826.5	ENSP00000356574.3	O00391-1
QSOX1	ENST00000367600.5 linkuse as main transcript	c.581A>C	p.Lys194Thr	missense_variant	5/13	1		ENSP00000356572.5	O00391-2
QSOX1	ENST00000392029.6 linkuse as main transcript	n.*10A>C		non_coding_transcript_exon_variant	4/8	5		ENSP00000375883.2	A8MXT8
QSOX1	ENST00000392029.6 linkuse as main transcript	n.*10A>C		3_prime_UTR_variant	4/8	5		ENSP00000375883.2	A8MXT8

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251490

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135918

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:

0.000139

Gnomad NFE exome

AF:

0.0000527

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000113

AC:

165

AN:

1461462

Hom.:

Cov.:

AF XY:

0.000100

AC XY:

AN XY:

727026

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:

0.0000936

Gnomad4 NFE exome

AF:

0.000141

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.0000227

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Jul 15, 2021

The c.581A>C (p.K194T) alteration is located in exon 5 (coding exon 5) of the QSOX1 gene. This alteration results from a A to C substitution at nucleotide position 581, causing the lysine (K) at amino acid position 194 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

0.10

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.042

T;.

Eigen

Benign

0.060

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

M;M

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.057

Sift

Benign

0.12

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.57

P;P

Vest4

0.21

MVP

0.29

MPC

0.17

ClinPred

0.32

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.53

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