chrX-48194185-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_175723.2(SSX5):c.224G>A(p.Arg75Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000778 in 1,207,823 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 39 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R75W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 21)

Exomes 𝑓: 0.000083 ( 0 hom. 39 hem. )

Consequence

SSX5
NM_175723.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.23

Publications

2 publications found

Variant links:

Genes affected

SSX5 (HGNC:11339): (SSX family member 5) 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 spontaneous humoral and cellular immune responses in cancer patients, and are potentially useful targets in cancer vaccine-based immunotherapy. While some of the related SSX genes are involved in t(X;18)(p11.2;q11.2) translocations that are characteristically found in all synovial sarcomas, this gene does not appear to be involved in such translocations. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2013]

SSX5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020476222).

BP6

Variant X-48194185-C-T is Benign according to our data. Variant chrX-48194185-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2257719.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 39 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175723.2. 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
	SSX5	NM_175723.2	MANE Select	c.224G>A	p.Arg75Gln	missense	Exon 4 of 8	NP_783729.1	O60225-1
	SSX5	NM_021015.4		c.347G>A	p.Arg116Gln	missense	Exon 5 of 9	NP_066295.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSX5	ENST00000347757.6	TSL:5 MANE Select	c.224G>A	p.Arg75Gln	missense	Exon 4 of 8	ENSP00000290558.1	O60225-1
	SSX5	ENST00000311798.5	TSL:5	c.347G>A	p.Arg116Gln	missense	Exon 5 of 9	ENSP00000312415.1	O60225-2

Frequencies

GnomAD3 genomes

AF:

0.0000273

AC:

AN:

110030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000331

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000787

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000709

AC:

AN:

183365

AF XY:

0.0000590

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.0000829

AC:

AN:

1097744

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

363214

show subpopulations

African (AFR)

AF:

0.0000758

AC:

AN:

26388

American (AMR)

AF:

0.0000284

AC:

AN:

35196

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19371

East Asian (EAS)

AF:

0.00

AC:

AN:

30183

South Asian (SAS)

AF:

0.000610

AC:

AN:

54124

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4131

European-Non Finnish (NFE)

AF:

0.0000582

AC:

AN:

841781

Other (OTH)

AF:

0.000130

AC:

AN:

46066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0000273

AC:

AN:

110079

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32331

show subpopulations

African (AFR)

AF:

0.0000330

AC:

AN:

30283

American (AMR)

AF:

0.00

AC:

AN:

10229

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2626

East Asian (EAS)

AF:

0.00

AC:

AN:

3489

South Asian (SAS)

AF:

0.000789

AC:

AN:

2534

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5712

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52808

Other (OTH)

AF:

0.00

AC:

AN:

1496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.0010

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.013

FATHMM_MKL

Benign

0.00033

LIST_S2

Benign

0.66

M_CAP

Benign

0.00096

MetaRNN

Benign

0.020

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

-5.2

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.35

REVEL

Benign

0.0030

Sift

Benign

0.42

Sift4G

Benign

0.38

Polyphen

0.0070

Vest4

0.072

MVP

0.081

MPC

0.017

ClinPred

0.019

GERP RS

-3.4

Varity_R

0.022

gMVP

0.022

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over