9-136209014-C-T

Variant names:

• chr9-136209014-C-T
• rs757951204
• NM_181701.4:c.1811G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_181701.4(QSOX2):​c.1811G>A​(p.Arg604Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,613,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: QSOX2 NM_181701.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0630
• Publications: 1 publications found

Genes affected

QSOX2 (HGNC:30249): (quiescin sulfhydryl oxidase 2) QSOX2 is a member of the sulfhydryl oxidase/quiescin-6 (Q6) family (QSOX1; MIM 603120) that regulates the sensitization of neuroblastoma cells for IFN-gamma (IFNG; MIM 147570)-induced cell death (Wittke et al., 2003 [PubMed 14633699]).[supplied by OMIM, Jun 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.033828437).
• BP6: Variant 9-136209014-C-T is Benign according to our data. Variant chr9-136209014-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2589742.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
QSOX2	NM_181701.4	c.1811G>A	p.Arg604Gln	missense_variant	Exon 12 of 12	ENST00000358701.10	NP_859052.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
QSOX2	ENST00000358701.10	c.1811G>A	p.Arg604Gln	missense_variant	Exon 12 of 12	2	NM_181701.4	ENSP00000351536.5
QSOX2	ENST00000706609.1	n.997G>A		non_coding_transcript_exon_variant	Exon 6 of 6

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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

GnomAD2 exomes AF: 0.0000518 AC: 13 AN: 251090 AF XY: 0.0000737

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000980

GnomAD4 exome AF: 0.0000335 AC: 49 AN: 1461642 Hom.: 0 Cov.: 34 AF XY: 0.0000426 AC XY: 31 AN XY: 727068

African (AFR) AF: 0.000149 AC: 5 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.0000234 AC: 26 AN: 1111872

Other (OTH) AF: 0.0000331 AC: 2 AN: 60382

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152220 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74360

African (AFR) AF: 0.0000241 AC: 1 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000203 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000577 AC: 7

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jun 26, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.088
DANN	Benign	0.37
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0061	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.4	N
PhyloP100		-0.063
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.024
Sift	Benign	1.0	T
Sift4G	Benign	0.56	T
Polyphen		0.0050	B
Vest4		0.052
MVP		0.13
MPC		0.25
ClinPred		0.0092	T
GERP RS		-0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.014
gMVP		0.18
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs757951204; hg19: chr9-139100860;