X-52645545-T-C

Variant names:

• chrX-52645545-T-C
• rs782584595
• NM_173358.2:c.467-2A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PVS1_Strong BP6_Moderate

The NM_173358.2(SSX7):​c.467-2A>G variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000037 (0 hom., 1 hem., cov: 20)
  • Exomes 𝑓: 0.000062 (1 hom. 25 hem.)
  • Failed GnomAD Quality Control
• Consequence: SSX7 NM_173358.2 splice_acceptor, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.28
• Publications: 0 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.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.18518518 fraction of the gene. Cryptic splice site detected, with MaxEntScore 3.6, offset of 34, new splice context is: aaacatgcctggacccacAGact. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
• BP6: Variant X-52645545-T-C is Benign according to our data. Variant chrX-52645545-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 797848.Status of the report is criteria_provided_single_submitter, 1 stars.

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.467-2A>G		splice_acceptor intron	N/A	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.467-2A>G		splice_acceptor intron	N/A	ENSP00000298181.5	Q7RTT5

Frequencies

GnomAD3 genomes AF: 0.0000373 AC: 4 AN: 107307 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00173

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000150 AC: 25 AN: 166578 AF XY: 0.000144

Gnomad AFR exome AF: 0.0000858

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: 0.000243

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000621 AC: 67 AN: 1079311 Hom.: 1 Cov.: 29 AF XY: 0.0000718 AC XY: 25 AN XY: 348001

African (AFR) AF: 0.0000386 AC: 1 AN: 25893

American (AMR) AF: 0.00 AC: 0 AN: 34568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18947

East Asian (EAS) AF: 0.00 AC: 0 AN: 30032

South Asian (SAS) AF: 0.00101 AC: 53 AN: 52414

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40281

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2830

European-Non Finnish (NFE) AF: 0.00000724 AC: 6 AN: 829080

Other (OTH) AF: 0.000155 AC: 7 AN: 45266

GnomAD4 genome AF: 0.0000373 AC: 4 AN: 107358 Hom.: 0 Cov.: 20 AF XY: 0.0000336 AC XY: 1 AN XY: 29720

African (AFR) AF: 0.00 AC: 0 AN: 29526

American (AMR) AF: 0.00 AC: 0 AN: 9804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2593

East Asian (EAS) AF: 0.00 AC: 0 AN: 3418

South Asian (SAS) AF: 0.00174 AC: 4 AN: 2299

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5433

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 214

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 51963

Other (OTH) AF: 0.00 AC: 0 AN: 1442

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.000175 AC: 21

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.93
CADD	Uncertain	24
DANN	Benign	0.81
FATHMM_MKL	Benign	0.0078	N
PhyloP100		1.3
GERP RS		0.58
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Benign	0.71
SpliceAI score (max)		1.0		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.91		Position offset: -12
DS_AL_spliceai		1.0		Position offset: -2

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

Other links and lift over

dbSNP: rs782584595; hg19: chrX-52674595;