Genetic Variant SSX5:p.Gln80Arg (chrX-48194170-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_175723.2(SSX5):c.239A>G(p.Gln80Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000729 in 1,097,759 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q80H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 21)

Exomes 𝑓: 0.0000073 ( 0 hom. 1 hem. )

Consequence

SSX5
NM_175723.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.08

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]

SSX5 links:

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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=0.089913905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSX5	NM_175723.2 link	c.239A>G	p.Gln80Arg	missense_variant	Exon 4 of 8	ENST00000347757.6	NP_783729.1	O60225-1
SSX5	NM_021015.4 link	c.362A>G	p.Gln121Arg	missense_variant	Exon 5 of 9		NP_066295.3	O60225-2
SSX5	XM_011543949.3 link	c.239A>G	p.Gln80Arg	missense_variant	Exon 4 of 8		XP_011542251.1	O60225-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSX5	ENST00000347757.6 link	c.239A>G	p.Gln80Arg	missense_variant	Exon 4 of 8	5	NM_175723.2	ENSP00000290558.1		O60225-1
SSX5	ENST00000311798.5 link	c.362A>G	p.Gln121Arg	missense_variant	Exon 5 of 9	5		ENSP00000312415.1		O60225-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000382

AC:

AN:

183370

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

67856

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000219

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:

0.00

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.00000729

AC:

AN:

1097759

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363233

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000227

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.362A>G (p.Q121R) alteration is located in exon 5 (coding exon 4) of the SSX5 gene. This alteration results from a A to G substitution at nucleotide position 362, causing the glutamine (Q) at amino acid position 121 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

0.089

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.041

DANN

Benign

0.93

DEOGEN2

Benign

0.047

T;.;T

FATHMM_MKL

Benign

0.0017

LIST_S2

Benign

0.85

.;T;T

M_CAP

Benign

0.0071

MetaRNN

Benign

0.090

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.;M

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.014

D;D;D

Sift4G

Benign

0.13

T;T;T

Polyphen

0.77

P;P;P

Vest4

0.052

MutPred

0.28

Gain of catalytic residue at Q80 (P = 0.0335);.;Gain of catalytic residue at Q80 (P = 0.0335);

MVP

0.081

MPC

0.029

ClinPred

0.33

GERP RS

-3.4

Varity_R

0.086

gMVP

0.022

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