X-52648342-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_173358.2(SSX7):​c.385G>A​(p.Ala129Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000735 in 1,210,336 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 26 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000089 ( 0 hom., 3 hem., cov: 23)
Exomes 𝑓: 0.000072 ( 0 hom. 23 hem. )

Consequence

SSX7
NM_173358.2 missense

Scores

16

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.08
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 Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.036903024).
BP6
Variant X-52648342-C-T is Benign according to our data. Variant chrX-52648342-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3170582.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SSX7NM_173358.2 linkc.385G>A p.Ala129Thr missense_variant Exon 6 of 8 ENST00000298181.6 NP_775494.1 Q7RTT5A0A024R019

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SSX7ENST00000298181.6 linkc.385G>A p.Ala129Thr missense_variant Exon 6 of 8 5 NM_173358.2 ENSP00000298181.5 Q7RTT5

Frequencies

GnomAD3 genomes
AF:
0.0000891
AC:
10
AN:
112280
Hom.:
0
Cov.:
23
AF XY:
0.0000871
AC XY:
3
AN XY:
34436
show subpopulations
Gnomad AFR
AF:
0.0000324
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:
0.000169
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000491
AC:
9
AN:
183376
Hom.:
0
AF XY:
0.0000295
AC XY:
2
AN XY:
67810
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000110
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000719
AC:
79
AN:
1098056
Hom.:
0
Cov.:
30
AF XY:
0.0000633
AC XY:
23
AN XY:
363416
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:
0.0000926
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
AF:
0.0000891
AC:
10
AN:
112280
Hom.:
0
Cov.:
23
AF XY:
0.0000871
AC XY:
3
AN XY:
34436
show subpopulations
Gnomad4 AFR
AF:
0.0000324
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:
0.000169
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000297
AC:
2
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Nov 03, 2023
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.078
BayesDel_addAF
Benign
-0.76
T
BayesDel_noAF
Benign
-1.1
CADD
Benign
0.0040
DANN
Benign
0.12
DEOGEN2
Benign
0.0019
T
FATHMM_MKL
Benign
0.00062
N
LIST_S2
Benign
0.82
T
M_CAP
Benign
0.0011
T
MetaRNN
Benign
0.037
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.8
L
PROVEAN
Benign
-0.70
N
REVEL
Benign
0.015
Sift
Benign
0.60
T
Sift4G
Benign
0.68
T
Polyphen
0.0030
B
Vest4
0.060
MVP
0.030
MPC
0.012
ClinPred
0.021
T
GERP RS
0.56
Varity_R
0.057
gMVP
0.021

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: rs370009445; hg19: chrX-52677392; API