rs782709420

Variant names:

• chrX-48410795-C-T
• rs782709420
• NM_001034832.5:c.139G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_001034832.5(SSX4B):​c.139G>A​(p.Val47Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000048 (0 hom. 0 hem.)
• Consequence: SSX4B NM_001034832.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.761
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07100916).
• BP6: Variant X-48410795-C-T is Benign according to our data. Variant chrX-48410795-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3170572.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034832.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSX4B	NM_001034832.5	MANE Select	c.139G>A	p.Val47Ile	missense	Exon 3 of 8	NP_001030004.1
	SSX4B	NM_001040612.4		c.139G>A	p.Val47Ile	missense	Exon 3 of 7	NP_001035702.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSX4B	ENST00000595235.6	TSL:1 MANE Select	c.139G>A	p.Val47Ile	missense	Exon 3 of 8	ENSP00000469394.1	O60224-1
	SSX4B	ENST00000619890.1	TSL:5	c.139G>A	p.Val47Ile	missense	Exon 3 of 7	ENSP00000481765.1	O60224-2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.0000181 AC: 3 AN: 165479 AF XY: 0.00

Gnomad AFR exome AF: 0.0000833

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000263

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000485 AC: 16 AN: 330004 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 76608

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 11848

American (AMR) AF: 0.00 AC: 0 AN: 11445

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5390

East Asian (EAS) AF: 0.0000873 AC: 1 AN: 11455

South Asian (SAS) AF: 0.00 AC: 0 AN: 24309

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 828

European-Non Finnish (NFE) AF: 0.0000653 AC: 15 AN: 229884

Other (OTH) AF: 0.00 AC: 0 AN: 14467

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000000439038), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.45
FATHMM_MKL	Benign	0.00029	N
LIST_S2	Benign	0.018	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-0.91	T
PhyloP100		0.76
PrimateAI	Uncertain	0.72	T
Sift4G	Benign	0.80	T
Vest4		0.034
MVP		0.081
ClinPred		0.013	T
GERP RS		0.43
gMVP		0.021
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs782709420; hg19: chrX-48270238;