X-52645523-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_173358.2(SSX7):​c.487G>A​(p.Ala163Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,198,558 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000047 ( 0 hom., 1 hem., cov: 20)
Exomes 𝑓: 0.000043 ( 0 hom. 15 hem. )

Consequence

SSX7
NM_173358.2 missense

Scores

1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.127
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.11124852).
BS2
High Hemizygotes in GnomAdExome4 at 15 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SSX7NM_173358.2 linkc.487G>A p.Ala163Thr missense_variant Exon 7 of 8 ENST00000298181.6 NP_775494.1 Q7RTT5A0A024R019

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SSX7ENST00000298181.6 linkc.487G>A p.Ala163Thr missense_variant Exon 7 of 8 5 NM_173358.2 ENSP00000298181.5 Q7RTT5

Frequencies

GnomAD3 genomes
AF:
0.0000467
AC:
5
AN:
107035
Hom.:
0
Cov.:
20
AF XY:
0.0000339
AC XY:
1
AN XY:
29467
show subpopulations
Gnomad AFR
AF:
0.0000682
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000577
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000172
AC:
3
AN:
174063
Hom.:
0
AF XY:
0.0000164
AC XY:
1
AN XY:
60855
show subpopulations
Gnomad AFR exome
AF:
0.0000828
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000257
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000431
AC:
47
AN:
1091523
Hom.:
0
Cov.:
30
AF XY:
0.0000418
AC XY:
15
AN XY:
358589
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000537
Gnomad4 OTH exome
AF:
0.0000437
GnomAD4 genome
AF:
0.0000467
AC:
5
AN:
107035
Hom.:
0
Cov.:
20
AF XY:
0.0000339
AC XY:
1
AN XY:
29467
show subpopulations
Gnomad4 AFR
AF:
0.0000682
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000577
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000214
Hom.:
1
Bravo
AF:
0.0000227
ExAC
AF:
0.00000826
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 12, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.487G>A (p.A163T) alteration is located in exon 7 (coding exon 6) of the SSX7 gene. This alteration results from a G to A substitution at nucleotide position 487, causing the alanine (A) at amino acid position 163 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-1.0
CADD
Benign
3.8
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0094
T
FATHMM_MKL
Benign
0.0032
N
LIST_S2
Benign
0.72
T
M_CAP
Benign
0.0017
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.55
N
PROVEAN
Benign
-1.4
N
REVEL
Benign
0.089
Sift
Benign
0.37
T
Sift4G
Benign
0.23
T
Polyphen
0.85
P
Vest4
0.17
MutPred
0.46
Gain of phosphorylation at A163 (P = 0.0249);
MVP
0.16
MPC
0.033
ClinPred
0.064
T
GERP RS
0.54
Varity_R
0.14
gMVP
0.013

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs782569072; hg19: chrX-52674573; API