chrX-52645457-C-A

Variant names:

• chrX-52645457-C-A
• rs146891115
• NM_173358.2:c.553G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_173358.2(SSX7):​c.553G>T​(p.Glu185*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: SSX7 NM_173358.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• Publications: 2 publications found

Genes affected

SSX7 (HGNC:19653): (SSX family member 7) 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 gene appears not to be involved in this type of chromosome translocation. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173358.2. 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
	SSX7	NM_173358.2	MANE Select	c.553G>T	p.Glu185*	stop_gained	Exon 7 of 8	NP_775494.1	Q7RTT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSX7	ENST00000298181.6	TSL:5 MANE Select	c.553G>T	p.Glu185*	stop_gained	Exon 7 of 8	ENSP00000298181.5	Q7RTT5

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000184 AC: 2 AN: 1084315 Hom.: 0 Cov.: 28 AF XY: 0.00000284 AC XY: 1 AN XY: 351535

⚠️ 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: 26114

American (AMR) AF: 0.00 AC: 0 AN: 34738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19144

East Asian (EAS) AF: 0.00 AC: 0 AN: 30159

South Asian (SAS) AF: 0.00 AC: 0 AN: 52927

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40445

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2841

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 832418

Other (OTH) AF: 0.0000439 AC: 2 AN: 45529

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 21

Alfa AF: 0.00 Hom.: 7

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	35
DANN	Uncertain	0.98
FATHMM_MKL	Benign	0.0089	N
PhyloP100		1.3
Vest4		0.015
GERP RS		0.54
Mutation Taster		=176/24	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: rs146891115; hg19: chrX-52674507;