X-48350080-C-G

Variant names:

• chrX-48350080-C-G
• rs1394365513
• NM_021014.4:c.373G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
• Consequence: SSX3 NM_021014.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433

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]

ACMG classification

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
SSX3	NM_021014.4	c.373G>C	p.Glu125Gln	missense_variant	Exon 6 of 8	ENST00000298396.7	NP_066294.1
SSX3	XM_011543885.3	c.373G>C	p.Glu125Gln	missense_variant	Exon 6 of 7		XP_011542187.1
SSX3	NR_176964.1	n.463G>C		non_coding_transcript_exon_variant	Exon 6 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSX3	ENST00000298396.7	c.373G>C	p.Glu125Gln	missense_variant	Exon 6 of 8	1	NM_021014.4	ENSP00000298396.2
SSX3	ENST00000612497.1	c.373G>C	p.Glu125Gln	missense_variant	Exon 5 of 5	5		ENSP00000480427.1
SSX3	ENST00000376893.7	c.373G>C	p.Glu125Gln	missense_variant	Exon 6 of 8	2		ENSP00000366090.3
SSX3	ENST00000376895.2	n.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

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

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

Other links and lift over

dbSNP: rs1394365513; hg19: chrX-48209515;