X-48410836-G-T

Variant names:

• chrX-48410836-G-T
• rs371037826
• NM_001034832.5:c.98C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001034832.5(SSX4B):​c.98C>A​(p.Ser33Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.00012 (0 hom. 0 hem.)
• Consequence: SSX4B NM_001034832.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.05

Genes affected

SSX4B (HGNC:16880): (SSX family member 4B) 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 spontaneously humoral and cellular immune responses in cancer patients, and are potentially useful targets in cancer vaccine-based immunotherapy. SSX1, SSX2 and SSX4 genes have been involved in the t(X;18) translocation characteristically found in all synovial sarcomas. This translocation results in the fusion of the synovial sarcoma translocation gene on chromosome 18 to one of the SSX genes on chromosome X. Chromosome Xp11 contains a segmental duplication resulting in two identical copies of synovial sarcoma, X breakpoint 4, SSX4 and SSX4B, in tail-to-tail orientation. This gene, SSX4B, represents the more centromeric copy. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17372376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSX4B	NM_001034832.5	c.98C>A	p.Ser33Tyr	missense_variant	Exon 3 of 8	ENST00000595235.6	NP_001030004.1
SSX4B	NM_001040612.4	c.98C>A	p.Ser33Tyr	missense_variant	Exon 3 of 7		NP_001035702.1
SSX4B	XM_017029613.2	c.98C>A	p.Ser33Tyr	missense_variant	Exon 3 of 7		XP_016885102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSX4B	ENST00000595235.6	c.98C>A	p.Ser33Tyr	missense_variant	Exon 3 of 8	1	NM_001034832.5	ENSP00000469394.1
SSX4B	ENST00000619890.1	c.98C>A	p.Ser33Tyr	missense_variant	Exon 3 of 7	5		ENSP00000481765.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.0000455 AC: 8 AN: 175920 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 62900

Gnomad AFR exome AF: 0.0000816

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000124 AC: 82 AN: 661991 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 160257

Gnomad4 AFR exome AF: 0.0000587

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: 0.000149

Gnomad4 OTH exome AF: 0.000113

GnomAD4 genome Cov.: 0

ESP6500AA AF: 0.000263 AC: 1

ESP6500EA AF: 0.000299 AC: 2

ExAC AF: 0.0000577 AC: 7

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.98C>A (p.S33Y) alteration is located in exon 3 (coding exon 2) of the SSX4B gene. This alteration results from a C to A substitution at nucleotide position 98, causing the serine (S) at amino acid position 33 to be replaced by a tyrosine (Y). 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	Uncertain	0.40
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	21
DANN	Uncertain	0.99
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.69	T
Sift4G	Pathogenic	0.0010	D;D
Vest4		0.58
MVP		0.030
ClinPred		0.12	T
GERP RS		0.71
gMVP		0.18

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

LitVar

Other links and lift over

dbSNP: rs371037826; hg19: chrX-48270279;