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

Variant summary

Our verdict is Benign. The variant received -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. 11/19 in silico tools predict 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

Publications

2 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 780693.Status of the report is criteria_provided_single_submitter, 1 stars.

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 the male GnomAd4 subpopulation. Median coverage is 21. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 gene

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.553G>A	p.Glu185Lys	missense	Exon 7 of 8	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.553G>A	p.Glu185Lys	missense	Exon 7 of 8	ENSP00000298181.5	Q7RTT5

Frequencies

GnomAD3 genomes

AF:

0.00744

AC:

806

AN:

108393

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00219

AC:

374

AN:

170963

AF XY:

0.00135

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 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

African (AFR)

AF:

0.0289

AC:

754

AN:

26104

American (AMR)

AF:

0.000835

AC:

AN:

34738

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19144

East Asian (EAS)

AF:

0.00

AC:

AN:

30159

South Asian (SAS)

AF:

0.0000378

AC:

AN:

52927

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40445

Middle Eastern (MID)

AF:

0.00106

AC:

AN:

2840

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

832417

Other (OTH)

AF:

0.00145

AC:

AN:

45529

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

122

153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00743

AC:

806

AN:

108438

Hom.:

Cov.:

AF XY:

0.00588

AC XY:

181

AN XY:

30768

show subpopulations

African (AFR)

AF:

0.0258

AC:

768

AN:

29794

American (AMR)

AF:

0.00301

AC:

AN:

9971

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2608

East Asian (EAS)

AF:

0.00

AC:

AN:

3449

South Asian (SAS)

AF:

0.000421

AC:

AN:

2376

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5525

Middle Eastern (MID)

AF:

0.00

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52372

Other (OTH)

AF:

0.00481

AC:

AN:

1456

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

101

126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.91

CADD

Benign

(source)

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

PhyloP100

1.3

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over