Genetic Variant SSX7:p.Ala129Thr (chrX-52648342-C-T) – ACMG Classification: Benign (-10 pts)

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

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]

SSX7 links:

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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
SSX7	NM_173358.2 link	c.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
SSX7	ENST00000298181.6 link	c.385G>A	p.Ala129Thr	missense_variant	Exon 6 of 8	5	NM_173358.2	ENSP00000298181.5		Q7RTT5

Frequencies

GnomAD3 genomes

AF:

0.0000891

AC:

AN:

112280

Hom.:

Cov.:

AF XY:

0.0000871

AC XY:

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:

AN:

183376

Hom.:

AF XY:

0.0000295

AC XY:

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:

AN:

1098056

Hom.:

Cov.:

AF XY:

0.0000633

AC XY:

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:

AN:

112280

Hom.:

Cov.:

AF XY:

0.0000871

AC XY:

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:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.0000165

AC:

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

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.0040

DANN

Benign

0.12

DEOGEN2

Benign

0.0019

FATHMM_MKL

Benign

0.00062

LIST_S2

Benign

0.82

M_CAP

Benign

0.0011

MetaRNN

Benign

0.037

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.8

PROVEAN

Benign

-0.70

REVEL

Benign

0.015

Sift

Benign

0.60

Sift4G

Benign

0.68

Polyphen

0.0030

Vest4

0.060

MVP

0.030

MPC

0.012

ClinPred

0.021

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over