X-48354013-T-C

Variant names:

• chrX-48354013-T-C
• NM_021014.4:c.266A>G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_021014.4(SSX3):​c.266A>G​(p.Asn89Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000456 in 1,095,875 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000046 (0 hom. 2 hem.)
• Consequence: SSX3 NM_021014.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.399

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15858492).
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSX3	NM_021014.4	c.266A>G	p.Asn89Ser	missense_variant	Exon 4 of 8	ENST00000298396.7	NP_066294.1
SSX3	XM_011543885.3	c.266A>G	p.Asn89Ser	missense_variant	Exon 4 of 7		XP_011542187.1
SSX3	NR_176964.1	n.356A>G		non_coding_transcript_exon_variant	Exon 4 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSX3	ENST00000298396.7	c.266A>G	p.Asn89Ser	missense_variant	Exon 4 of 8	1	NM_021014.4	ENSP00000298396.2
SSX3	ENST00000612497.1	c.266A>G	p.Asn89Ser	missense_variant	Exon 3 of 5	5		ENSP00000480427.1
SSX3	ENST00000376893.7	c.266A>G	p.Asn89Ser	missense_variant	Exon 4 of 8	2		ENSP00000366090.3

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 0.00000456 AC: 5 AN: 1095875 Hom.: 0 Cov.: 30 AF XY: 0.00000553 AC XY: 2 AN XY: 361457

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: 0.00000595

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 21

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.266A>G (p.N89S) alteration is located in exon 4 (coding exon 3) of the SSX3 gene. This alteration results from a A to G substitution at nucleotide position 266, causing the asparagine (N) at amino acid position 89 to be replaced by a serine (S). 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	0.088
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	8.7
DANN	Uncertain	0.97
DEOGEN2	Benign	0.030	T;.;.
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.00088	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M;M;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.4	N;D;.
REVEL	Benign	0.022
Sift	Benign	0.23	T;T;.
Sift4G	Benign	0.076	T;T;D
Polyphen		0.90	P;.;.
Vest4		0.079
MutPred		0.27		Gain of loop (P = 0.0502);Gain of loop (P = 0.0502);Gain of loop (P = 0.0502);
MVP		0.13
MPC		0.040
ClinPred		0.44	T
GERP RS		-0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.053
gMVP		0.026

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-48213448;