Genetic Variant SSX3:p.Glu125Lys (chrX-48350080-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021014.4(SSX3):c.373G>A(p.Glu125Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,209 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. 15/21 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: 9.1e-7 ( 0 hom. 1 hem. )

Consequence

SSX3
NM_021014.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.433

Publications

0 publications found

Variant links:

Genes affected

SSX3 (HGNC:11337): (SSX family member 3) 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. [provided by RefSeq, Jul 2013]

SSX3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.050864488).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021014.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSX3	NM_021014.4	MANE Select	c.373G>A	p.Glu125Lys	missense	Exon 6 of 8	NP_066294.1	Q99909-1
	SSX3	NR_176964.1		n.463G>A		non_coding_transcript_exon	Exon 6 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SSX3	ENST00000298396.7	TSL:1 MANE Select	c.373G>A	p.Glu125Lys	missense	Exon 6 of 8	ENSP00000298396.2	Q99909-1
SSX3	ENST00000612497.1	TSL:5	c.373G>A	p.Glu125Lys	missense	Exon 5 of 5	ENSP00000480427.1	A0A087WWQ6
SSX3	ENST00000376893.7	TSL:2	c.373G>A	p.Glu125Lys	missense	Exon 6 of 8	ENSP00000366090.3	Q99909-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000545

AC:

AN:

183469

AF XY:

0.0000147

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 FIN exome

AF:

0.0000625

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1098209

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363567

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26401

American (AMR)

AF:

0.00

AC:

AN:

35204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19385

East Asian (EAS)

AF:

0.00

AC:

AN:

30205

South Asian (SAS)

AF:

0.00

AC:

AN:

54141

European-Finnish (FIN)

AF:

0.0000247

AC:

AN:

40533

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

842107

Other (OTH)

AF:

0.00

AC:

AN:

46096

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.45

(source)

DANN

Benign

0.26

DEOGEN2

Benign

0.018

FATHMM_MKL

Benign

0.0020

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0016

MetaRNN

Benign

0.051

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

PhyloP100

-0.43

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.1

REVEL

Benign

0.027

Sift

Benign

0.73

Sift4G

Benign

0.72

Polyphen

0.0030

Vest4

0.19

MutPred

0.25

Gain of ubiquitination at E125 (P = 0.0022)

MVP

0.061

MPC

0.023

ClinPred

0.072

GERP RS

-2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.038

gMVP

0.063

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over