chrX-48187720-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_175723.2(SSX5):​c.478G>A​(p.Gly160Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 23)
Exomes 𝑓: 0.0000027 ( 0 hom. 1 hem. )
Failed GnomAD Quality Control

Consequence

SSX5
NM_175723.2 missense

Scores

3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.88
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11271697).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SSX5NM_175723.2 linkc.478G>A p.Gly160Arg missense_variant Exon 7 of 8 ENST00000347757.6 NP_783729.1 O60225-1
SSX5NM_021015.4 linkc.601G>A p.Gly201Arg missense_variant Exon 8 of 9 NP_066295.3 O60225-2
SSX5XM_011543949.3 linkc.478G>A p.Gly160Arg missense_variant Exon 7 of 8 XP_011542251.1 O60225-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SSX5ENST00000347757.6 linkc.478G>A p.Gly160Arg missense_variant Exon 7 of 8 5 NM_175723.2 ENSP00000290558.1 O60225-1
SSX5ENST00000311798.5 linkc.601G>A p.Gly201Arg missense_variant Exon 8 of 9 5 ENSP00000312415.1 O60225-2
SSX5ENST00000403001.3 linkn.298G>A non_coding_transcript_exon_variant Exon 3 of 4 5

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000274
AC:
3
AN:
1095417
Hom.:
0
Cov.:
30
AF XY:
0.00000276
AC XY:
1
AN XY:
361935
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:
0.00000357
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 22, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.601G>A (p.G201R) alteration is located in exon 8 (coding exon 7) of the SSX5 gene. This alteration results from a G to A substitution at nucleotide position 601, causing the glycine (G) at amino acid position 201 to be replaced by an arginine (R). 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
0.12
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.14
DANN
Uncertain
0.98
DEOGEN2
Benign
0.018
T;.;T;.
FATHMM_MKL
Benign
0.0011
N
LIST_S2
Benign
0.70
.;T;T;T
M_CAP
Benign
0.0015
T
MetaRNN
Benign
0.11
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
L;.;L;.
PrimateAI
Benign
0.25
T
PROVEAN
Uncertain
-2.5
N;N;N;N
REVEL
Benign
0.031
Sift
Benign
0.24
T;T;T;D
Sift4G
Uncertain
0.0060
D;D;D;D
Polyphen
0.029
B;B;B;.
Vest4
0.099
MutPred
0.51
Gain of glycosylation at P157 (P = 0.0466);.;Gain of glycosylation at P157 (P = 0.0466);.;
MVP
0.40
MPC
0.017
ClinPred
0.34
T
GERP RS
-2.1
Varity_R
0.13
gMVP
0.016

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-48047156; API