X-48194150-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_175723.2(SSX5):​c.259G>A​(p.Asp87Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000621 in 1,207,907 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 20 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 0 hem., cov: 21)
Exomes 𝑓: 0.000064 ( 0 hom. 20 hem. )

Consequence

SSX5
NM_175723.2 missense

Scores

2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.649
Variant links:
Genes affected
SSX5 (HGNC:11339): (SSX family member 5) The product of this gene belongs to the family of highly homologous synovial sarcoma X (SSX) breakpoint proteins. These proteins may function as transcriptional repressors. They are also capable of eliciting spontaneous humoral and cellular immune responses in cancer patients, and are potentially useful targets in cancer vaccine-based immunotherapy. While some of the related SSX genes are involved in t(X;18)(p11.2;q11.2) translocations that are characteristically found in all synovial sarcomas, this gene does not appear to be involved in such translocations. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.13108355).
BS2
High Hemizygotes in GnomAdExome4 at 20 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SSX5NM_175723.2 linkc.259G>A p.Asp87Asn missense_variant Exon 4 of 8 ENST00000347757.6 NP_783729.1 O60225-1
SSX5NM_021015.4 linkc.382G>A p.Asp128Asn missense_variant Exon 5 of 9 NP_066295.3 O60225-2
SSX5XM_011543949.3 linkc.259G>A p.Asp87Asn missense_variant Exon 4 of 8 XP_011542251.1 O60225-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SSX5ENST00000347757.6 linkc.259G>A p.Asp87Asn missense_variant Exon 4 of 8 5 NM_175723.2 ENSP00000290558.1 O60225-1
SSX5ENST00000311798.5 linkc.382G>A p.Asp128Asn missense_variant Exon 5 of 9 5 ENSP00000312415.1 O60225-2

Frequencies

GnomAD3 genomes
AF:
0.0000454
AC:
5
AN:
110164
Hom.:
0
Cov.:
21
AF XY:
0.00
AC XY:
0
AN XY:
32408
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:
0.0000757
Gnomad OTH
AF:
0.000674
GnomAD3 exomes
AF:
0.0000382
AC:
7
AN:
183347
Hom.:
0
AF XY:
0.0000295
AC XY:
2
AN XY:
67857
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:
0.00
Gnomad NFE exome
AF:
0.0000489
Gnomad OTH exome
AF:
0.000663
GnomAD4 exome
AF:
0.0000638
AC:
70
AN:
1097743
Hom.:
0
Cov.:
31
AF XY:
0.0000551
AC XY:
20
AN XY:
363211
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:
0.0000796
Gnomad4 OTH exome
AF:
0.0000651
GnomAD4 genome
AF:
0.0000454
AC:
5
AN:
110164
Hom.:
0
Cov.:
21
AF XY:
0.00
AC XY:
0
AN XY:
32408
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:
0.0000757
Gnomad4 OTH
AF:
0.000674
Alfa
AF:
0.000130
Hom.:
1
Bravo
AF:
0.0000227

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 23, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.382G>A (p.D128N) alteration is located in exon 5 (coding exon 4) of the SSX5 gene. This alteration results from a G to A substitution at nucleotide position 382, causing the aspartic acid (D) at amino acid position 128 to be replaced by an asparagine (N). 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
0.11
BayesDel_addAF
Benign
-0.72
T
BayesDel_noAF
Benign
-1.1
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Benign
0.028
T;.;T
FATHMM_MKL
Benign
0.0072
N
LIST_S2
Benign
0.79
.;T;T
M_CAP
Benign
0.00083
T
MetaRNN
Benign
0.13
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.2
M;.;M
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-2.1
N;N;N
REVEL
Benign
0.033
Sift
Benign
0.16
T;T;T
Sift4G
Benign
0.18
T;T;T
Polyphen
0.97
D;P;D
Vest4
0.10
MutPred
0.32
Loss of catalytic residue at D87 (P = 0.1062);.;Loss of catalytic residue at D87 (P = 0.1062);
MVP
0.095
MPC
0.086
ClinPred
0.48
T
GERP RS
0.82
Varity_R
0.055
gMVP
0.028

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.

Other links and lift over

dbSNP: rs1361080260; hg19: chrX-48053586; API