Genetic Variant SSX7:p.Glu185Lys (chrX-52645457-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_173358.2(SSX7):c.553G>A(p.Glu185Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,192,741 control chromosomes in the GnomAD database, including 11 homozygotes. There are 381 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0074 ( 6 hom., 181 hem., cov: 21)

Exomes 𝑓: 0.00080 ( 5 hom. 200 hem. )

Consequence

SSX7
NM_173358.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.34

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041498244).

BP6

Variant X-52645457-C-T is Benign according to our data. Variant chrX-52645457-C-T is described in ClinVar as [Benign]. Clinvar id is 780693.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-52645457-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00743 (806/108438) while in subpopulation AFR AF= 0.0258 (768/29794). AF 95% confidence interval is 0.0243. There are 6 homozygotes in gnomad4. There are 181 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSX7	NM_173358.2 link	c.553G>A	p.Glu185Lys	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
SSX7	ENST00000298181.6 link	c.553G>A	p.Glu185Lys	missense_variant	Exon 7 of 8	5	NM_173358.2	ENSP00000298181.5		Q7RTT5

Frequencies

GnomAD3 genomes

AF:

0.00744

AC:

806

AN:

108393

Hom.:

Cov.:

AF XY:

0.00593

AC XY:

182

AN XY:

30713

show subpopulations

Gnomad AFR

AF:

0.0259

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

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:

0.00

Gnomad OTH

AF:

0.00487

GnomAD3 exomes

AF:

0.00219

AC:

374

AN:

170963

Hom.:

AF XY:

0.00135

AC XY:

AN XY:

56893

show subpopulations

Gnomad AFR exome

AF:

0.0266

Gnomad AMR exome

AF:

0.000817

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000130

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000389

Gnomad OTH exome

AF:

0.000238

GnomAD4 exome

AF:

0.000799

AC:

866

AN:

1084303

Hom.:

Cov.:

AF XY:

0.000569

AC XY:

200

AN XY:

351527

show subpopulations

Gnomad4 AFR exome

AF:

0.0289

Gnomad4 AMR exome

AF:

0.000835

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000378

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.00145

GnomAD4 genome

AF:

0.00743

AC:

806

AN:

108438

Hom.:

Cov.:

AF XY:

0.00588

AC XY:

181

AN XY:

30768

show subpopulations

Gnomad4 AFR

AF:

0.0258

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000421

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00481

Alfa

AF:

0.00166

Hom.:

Bravo

AF:

0.00852

ESP6500AA

AF:

0.0237

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00236

AC:

286

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.91

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

FATHMM_MKL

Benign

0.0070

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.0041

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.071

Sift

Uncertain

0.0050

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.34

MVP

0.030

MPC

0.085

ClinPred

0.049

GERP RS

0.54

Varity_R

0.93

gMVP

0.039

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