NM_001034832.5:c.118A>G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.118A>G	p.Met40Val	missense	Exon 3 of 8	NP_001030004.1
	SSX4B	NM_001040612.4		c.118A>G	p.Met40Val	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.118A>G	p.Met40Val	missense	Exon 3 of 8	ENSP00000469394.1	O60224-1
	SSX4B	ENST00000619890.1	TSL:5	c.118A>G	p.Met40Val	missense	Exon 3 of 7	ENSP00000481765.1	O60224-2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.0000660 AC: 11 AN: 166621 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

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

⚠️ 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: 13692

American (AMR) AF: 0.00 AC: 0 AN: 12270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6925

East Asian (EAS) AF: 0.00 AC: 0 AN: 13791

South Asian (SAS) AF: 0.000245 AC: 7 AN: 28580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22091

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1139

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 332191

Other (OTH) AF: 0.00 AC: 0 AN: 19227

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00149986), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ExAC AF: 0.000140 AC: 17

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	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
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.39
PrimateAI	Uncertain	0.66	T
Sift4G	Uncertain	0.0070	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

Other links and lift over

dbSNP: rs782670402; hg19: chrX-48270259;