Variant chr1-180175997-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002826.5(QSOX1):c.479C>T(p.Thr160Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000347 in 1,601,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

QSOX1
NM_002826.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.451

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.014998734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
QSOX1	NM_002826.5 linkuse as main transcript	c.479C>T	p.Thr160Met	missense_variant	4/12	ENST00000367602.8
QSOX1	NM_001004128.3 linkuse as main transcript	c.479C>T	p.Thr160Met	missense_variant	4/13
QSOX1	XM_047426230.1 linkuse as main transcript	c.479C>T	p.Thr160Met	missense_variant	4/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
QSOX1	ENST00000367602.8 linkuse as main transcript	c.479C>T	p.Thr160Met	missense_variant	4/12	1	NM_002826.5	P2	O00391-1
QSOX1	ENST00000367600.5 linkuse as main transcript	c.479C>T	p.Thr160Met	missense_variant	4/13	1		A2	O00391-2
QSOX1	ENST00000392029.6 linkuse as main transcript	c.412+631C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000407

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000391

AC:

AN:

227682

Hom.:

AF XY:

0.000440

AC XY:

AN XY:

122772

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000283

Gnomad ASJ exome

AF:

0.00167

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000613

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000447

Gnomad OTH exome

AF:

0.000179

GnomAD4 exome

AF:

0.000341

AC:

494

AN:

1449428

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

261

AN XY:

719574

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.000282

Gnomad4 ASJ exome

AF:

0.00248

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.000621

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000297

Gnomad4 OTH exome

AF:

0.000434

GnomAD4 genome

AF:

0.000407

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000444

Hom.:

Bravo

AF:

0.000385

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000347

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

Feb 14, 2023

The c.479C>T (p.T160M) alteration is located in exon 4 (coding exon 4) of the QSOX1 gene. This alteration results from a C to T substitution at nucleotide position 479, causing the threonine (T) at amino acid position 160 to be replaced by a methionine (M). 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

0.092

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.19

T;.

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.048

Sift

Benign

0.17

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.66

P;P

Vest4

0.17

MVP

0.22

MPC

0.14

ClinPred

0.037

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.057

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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