9-136208887-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_181701.4(QSOX2):​c.1938C>T​(p.Gly646Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00248 in 1,613,954 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0026 ( 54 hom. )

Consequence

QSOX2
NM_181701.4 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: 0.182
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 9-136208887-G-A is Benign according to our data. Variant chr9-136208887-G-A is described in ClinVar as [Benign]. Clinvar id is 771171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.182 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00256 (3744/1461684) while in subpopulation SAS AF= 0.0203 (1748/86258). AF 95% confidence interval is 0.0195. There are 54 homozygotes in gnomad4_exome. There are 2282 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
QSOX2NM_181701.4 linkc.1938C>T p.Gly646Gly synonymous_variant 12/12 ENST00000358701.10 NP_859052.3 Q6ZRP7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
QSOX2ENST00000358701.10 linkc.1938C>T p.Gly646Gly synonymous_variant 12/122 NM_181701.4 ENSP00000351536.5 Q6ZRP7
QSOX2ENST00000706609.1 linkn.1124C>T non_coding_transcript_exon_variant 6/6

Frequencies

GnomAD3 genomes
AF:
0.00170
AC:
259
AN:
152152
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00124
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0139
Gnomad SAS
AF:
0.0172
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00104
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00402
AC:
1009
AN:
251134
Hom.:
13
AF XY:
0.00493
AC XY:
669
AN XY:
135768
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00121
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0114
Gnomad SAS exome
AF:
0.0195
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00120
Gnomad OTH exome
AF:
0.00375
GnomAD4 exome
AF:
0.00256
AC:
3744
AN:
1461684
Hom.:
54
Cov.:
30
AF XY:
0.00314
AC XY:
2282
AN XY:
727136
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.00107
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0138
Gnomad4 SAS exome
AF:
0.0203
Gnomad4 FIN exome
AF:
0.0000376
Gnomad4 NFE exome
AF:
0.00104
Gnomad4 OTH exome
AF:
0.00313
GnomAD4 genome
AF:
0.00170
AC:
259
AN:
152270
Hom.:
2
Cov.:
32
AF XY:
0.00219
AC XY:
163
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.000217
Gnomad4 AMR
AF:
0.00124
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0139
Gnomad4 SAS
AF:
0.0172
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00104
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00150
Hom.:
0
Bravo
AF:
0.00133
Asia WGS
AF:
0.0110
AC:
38
AN:
3478
EpiCase
AF:
0.00174
EpiControl
AF:
0.00136

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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 03, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
4.6
DANN
Benign
0.54
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs151235947; hg19: chr9-139100733; COSMIC: COSV62393863; COSMIC: COSV62393863; API