X-48410044-G-C

Variant names:

• chrX-48410044-G-C
• rs782696222
• NM_001034832.5:c.214C>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001034832.5(SSX4B):​c.214C>G​(p.Arg72Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: SSX4B NM_001034832.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.70

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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01072669).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSX4B	NM_001034832.5	c.214C>G	p.Arg72Gly	missense_variant	Exon 4 of 8	ENST00000595235.6	NP_001030004.1
SSX4B	NM_001040612.4	c.214C>G	p.Arg72Gly	missense_variant	Exon 4 of 7		NP_001035702.1
SSX4B	XM_017029613.2	c.214C>G	p.Arg72Gly	missense_variant	Exon 4 of 7		XP_016885102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSX4B	ENST00000595235.6	c.214C>G	p.Arg72Gly	missense_variant	Exon 4 of 8	1	NM_001034832.5	ENSP00000469394.1
SSX4B	ENST00000619890.1	c.214C>G	p.Arg72Gly	missense_variant	Exon 4 of 7	5		ENSP00000481765.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.0000569 AC: 3 AN: 52752 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 11670

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000764

Gnomad SAS exome AF: 0.000248

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ExAC AF: 0.0000682 AC: 5

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.214C>G (p.R72G) alteration is located in exon 4 (coding exon 3) of the SSX4B gene. This alteration results from a C to G substitution at nucleotide position 214, causing the arginine (R) at amino acid position 72 to be replaced by a glycine (G). 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	0.13
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.011
DANN	Benign	0.38
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.00091	T
MetaRNN	Benign	0.011	T;T
MetaSVM	Benign	-0.93	T
PrimateAI	Uncertain	0.50	T
Sift4G	Benign	0.38	T;T
Vest4		0.042
MVP		0.014
ClinPred		0.018	T
GERP RS		-2.8
gMVP		0.035

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: rs782696222; hg19: chrX-48269487;