X-52645457-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173358.2(SSX7):​c.553G>C​(p.Glu185Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E185K) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000018 (0 hom. 2 hem.)
  • Failed GnomAD Quality Control
• Consequence: SSX7 NM_173358.2 missense
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29521486).

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>C	p.Glu185Gln	missense	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>C	p.Glu185Gln	missense	Exon 7 of 8	ENSP00000298181.5	Q7RTT5

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD2 exomes AF: 0.0000117 AC: 2 AN: 170963 AF XY: 0.0000352

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: 0.000129

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000184 AC: 2 AN: 1084315 Hom.: 0 Cov.: 28 AF XY: 0.00000569 AC XY: 2 AN XY: 351535

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: 0.0000332 AC: 1 AN: 30159

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

European-Finnish (FIN) AF: 0.0000247 AC: 1 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: 0.00 AC: 0 AN: 45529

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Benign	0.0095	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.3
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.081
Sift	Uncertain	0.0070	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.33
MutPred		0.60		Gain of relative solvent accessibility (P = 0.1684)
MVP		0.030
MPC		0.085
ClinPred		0.40	T
GERP RS		0.54
Varity_R		0.80
gMVP		0.029
Mutation Taster		=99/1	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;