chrX-48187720-C-T

Variant names:

• chrX-48187720-C-T
• NM_175723.2:c.478G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.88

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]

ACMG classification

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
SSX5	NM_175723.2	c.478G>A	p.Gly160Arg	missense_variant	Exon 7 of 8	ENST00000347757.6	NP_783729.1
SSX5	NM_021015.4	c.601G>A	p.Gly201Arg	missense_variant	Exon 8 of 9		NP_066295.3
SSX5	XM_011543949.3	c.478G>A	p.Gly160Arg	missense_variant	Exon 7 of 8		XP_011542251.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSX5	ENST00000347757.6	c.478G>A	p.Gly160Arg	missense_variant	Exon 7 of 8	5	NM_175723.2	ENSP00000290558.1
SSX5	ENST00000311798.5	c.601G>A	p.Gly201Arg	missense_variant	Exon 8 of 9	5		ENSP00000312415.1
SSX5	ENST00000403001.3	n.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

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

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;