X-48410816-T-C

Variant names:

• chrX-48410816-T-C
• rs782670402
• NM_001034832.5:c.118A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001034832.5(SSX4B):​c.118A>G​(p.Met40Val) 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: 0.000016 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: SSX4B NM_001034832.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.393

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSX4B	NM_001034832.5	c.118A>G	p.Met40Val	missense_variant	Exon 3 of 8	ENST00000595235.6	NP_001030004.1
SSX4B	NM_001040612.4	c.118A>G	p.Met40Val	missense_variant	Exon 3 of 7		NP_001035702.1
SSX4B	XM_017029613.2	c.118A>G	p.Met40Val	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.118A>G	p.Met40Val	missense_variant	Exon 3 of 8	1	NM_001034832.5	ENSP00000469394.1
SSX4B	ENST00000619890.1	c.118A>G	p.Met40Val	missense_variant	Exon 3 of 7	5		ENSP00000481765.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000156 AC: 7 AN: 449906 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 109022

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: 0.000245

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ExAC AF: 0.000140 AC: 17

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 31, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.118A>G (p.M40V) alteration is located in exon 3 (coding exon 2) of the SSX4B gene. This alteration results from a A to G substitution at nucleotide position 118, causing the methionine (M) at amino acid position 40 to be replaced by a valine (V). 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	0.42
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.96
CADD	Benign	14
DANN	Benign	0.74
FATHMM_MKL	Benign	0.0038	N
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.056	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.66	T
Sift4G	Uncertain	0.0070	D;D
Vest4		0.091
MVP		0.14
ClinPred		0.014	T
GERP RS		-2.6
gMVP		0.066

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.32		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs782670402; hg19: chrX-48270259;