X-48192247-C-G

Variant names:

• chrX-48192247-C-G
• rs782286564
• NM_175723.2:c.315G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_175723.2(SSX5):​c.315G>C​(p.Gln105His) 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. 15/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: SSX5 NM_175723.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274
• Publications: 2 publications found

Genes affected

SSX5 (HGNC:11339): (SSX family member 5) 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 spontaneous humoral and cellular immune responses in cancer patients, and are potentially useful targets in cancer vaccine-based immunotherapy. While some of the related SSX genes are involved in t(X;18)(p11.2;q11.2) translocations that are characteristically found in all synovial sarcomas, this gene does not appear to be involved in such translocations. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06355375).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175723.2. 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
	SSX5	NM_175723.2	MANE Select	c.315G>C	p.Gln105His	missense	Exon 5 of 8	NP_783729.1	O60225-1
	SSX5	NM_021015.4		c.438G>C	p.Gln146His	missense	Exon 6 of 9	NP_066295.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSX5	ENST00000347757.6	TSL:5 MANE Select	c.315G>C	p.Gln105His	missense	Exon 5 of 8	ENSP00000290558.1	O60225-1
	SSX5	ENST00000311798.5	TSL:5	c.438G>C	p.Gln146His	missense	Exon 6 of 9	ENSP00000312415.1	O60225-2
	SSX5	ENST00000403001.3	TSL:5	n.135G>C		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000109 AC: 2 AN: 183246 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000144

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: 9.11e-7 AC: 1 AN: 1097797 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363323

African (AFR) AF: 0.00 AC: 0 AN: 26386

American (AMR) AF: 0.00 AC: 0 AN: 35196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19377

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30196

South Asian (SAS) AF: 0.00 AC: 0 AN: 54123

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4096

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841827

Other (OTH) AF: 0.00 AC: 0 AN: 46066

GnomAD4 genome Cov.: 23

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.7
DANN	Benign	0.94
DEOGEN2	Benign	0.028	T
FATHMM_MKL	Benign	0.0086	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.27
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.0080
Sift	Benign	0.089	T
Sift4G	Uncertain	0.025	D
Polyphen		0.026	B
Vest4		0.11
MutPred		0.20		Loss of loop (P = 0.1258)
MVP		0.16
MPC		0.018
ClinPred		0.023	T
GERP RS		0.24
Varity_R		0.13
gMVP		0.071
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: rs782286564; hg19: chrX-48051683;