Variant 1-180154998-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.91C>T(p.Pro31Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000957 in 1,357,926 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: not found (cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

QSOX1
NM_002826.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.723

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 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=0.042387903).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
QSOX1	NM_002826.5 linkuse as main transcript	c.91C>T	p.Pro31Ser	missense_variant	1/12	ENST00000367602.8
QSOX1	NM_001004128.3 linkuse as main transcript	c.91C>T	p.Pro31Ser	missense_variant	1/13
QSOX1	XM_047426230.1 linkuse as main transcript	c.91C>T	p.Pro31Ser	missense_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
QSOX1	ENST00000367602.8 linkuse as main transcript	c.91C>T	p.Pro31Ser	missense_variant	1/12	1	NM_002826.5	P2	O00391-1
QSOX1	ENST00000367600.5 linkuse as main transcript	c.91C>T	p.Pro31Ser	missense_variant	1/13	1		A2	O00391-2
QSOX1	ENST00000392029.6 linkuse as main transcript	c.91C>T	p.Pro31Ser	missense_variant, NMD_transcript_variant	1/8	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000957

AC:

AN:

1357926

Hom.:

Cov.:

AF XY:

0.00000448

AC XY:

AN XY:

669544

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:

0.0000112

Gnomad4 OTH exome

AF:

0.0000177

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Sep 29, 2023

The c.91C>T (p.P31S) alteration is located in exon 1 (coding exon 1) of the QSOX1 gene. This alteration results from a C to T substitution at nucleotide position 91, causing the proline (P) at amino acid position 31 to be replaced by a serine (S). 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

0.093

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0088

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.062

MetaRNN

Benign

0.042

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

0.87

N;N

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.050

N;N

REVEL

Benign

0.027

Sift

Benign

0.65

T;T

Sift4G

Benign

0.69

T;T

Polyphen

0.0080

B;B

Vest4

0.086

MutPred

0.26

Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);

MVP

0.088

MPC

0.14

ClinPred

0.092

GERP RS

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.022

gMVP

0.43

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