X-48350080-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021014.4(SSX3):​c.373G>C​(p.Glu125Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000894 in 111,916 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E125K) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0000089 ( 0 hom., 0 hem., cov: 23)

Consequence

SSX3
NM_021014.4 missense

Scores

17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.433
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05554104).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SSX3NM_021014.4 linkc.373G>C p.Glu125Gln missense_variant Exon 6 of 8 ENST00000298396.7 NP_066294.1 Q99909-1
SSX3XM_011543885.3 linkc.373G>C p.Glu125Gln missense_variant Exon 6 of 7 XP_011542187.1 Q99909-2A0A024R1B1
SSX3NR_176964.1 linkn.463G>C non_coding_transcript_exon_variant Exon 6 of 9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SSX3ENST00000298396.7 linkc.373G>C p.Glu125Gln missense_variant Exon 6 of 8 1 NM_021014.4 ENSP00000298396.2 Q99909-1
SSX3ENST00000612497.1 linkc.373G>C p.Glu125Gln missense_variant Exon 5 of 5 5 ENSP00000480427.1 A0A087WWQ6
SSX3ENST00000376893.7 linkc.373G>C p.Glu125Gln missense_variant Exon 6 of 8 2 ENSP00000366090.3 Q99909-2
SSX3ENST00000376895.2 linkn.191G>C non_coding_transcript_exon_variant Exon 2 of 4 5

Frequencies

GnomAD3 genomes
AF:
0.00000894
AC:
1
AN:
111916
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34082
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:
0.0000188
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
32
GnomAD4 genome
AF:
0.00000894
AC:
1
AN:
111916
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34082
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:
0.0000188
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.37
DANN
Benign
0.13
DEOGEN2
Benign
0.011
T;.;.
FATHMM_MKL
Benign
0.0019
N
LIST_S2
Benign
0.65
T;T;T
M_CAP
Benign
0.0012
T
MetaRNN
Benign
0.056
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
L;L;.
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-0.47
N;N;.
REVEL
Benign
0.012
Sift
Benign
0.44
T;T;.
Sift4G
Benign
0.53
T;T;T
Polyphen
0.0
B;.;.
Vest4
0.11
MutPred
0.14
Gain of loop (P = 0.069);Gain of loop (P = 0.069);Gain of loop (P = 0.069);
MVP
0.095
MPC
0.021
ClinPred
0.050
T
GERP RS
-2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.1
Varity_R
0.061
gMVP
0.050

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: rs1394365513; hg19: chrX-48209515; API