Genetic Variant SSX5:p.Arg72His (chrX-48194194-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_175723.2(SSX5):c.215G>A(p.Arg72His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,207,797 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 57 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., 3 hem., cov: 21)

Exomes 𝑓: 0.00014 ( 0 hom. 54 hem. )

Consequence

SSX5
NM_175723.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.660

Publications

8 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04406482).

BS2

High Hemizygotes in GnomAd4 at 3 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.215G>A	p.Arg72His	missense	Exon 4 of 8	NP_783729.1	O60225-1
	SSX5	NM_021015.4		c.338G>A	p.Arg113His	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.215G>A	p.Arg72His	missense	Exon 4 of 8	ENSP00000290558.1	O60225-1
	SSX5	ENST00000311798.5	TSL:5	c.338G>A	p.Arg113His	missense	Exon 5 of 9	ENSP00000312415.1	O60225-2

Frequencies

GnomAD3 genomes

AF:

0.000109

AC:

AN:

110186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000132

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:

0.000151

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000818

AC:

AN:

183358

AF XY:

0.000103

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000134

Gnomad EAS exome

AF:

0.000216

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000978

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000140

AC:

154

AN:

1097611

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

363087

show subpopulations

African (AFR)

AF:

0.0000758

AC:

AN:

26387

American (AMR)

AF:

0.00

AC:

AN:

35196

Ashkenazi Jewish (ASJ)

AF:

0.0000516

AC:

AN:

19370

East Asian (EAS)

AF:

0.000365

AC:

AN:

30178

South Asian (SAS)

AF:

0.0000554

AC:

AN:

54127

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40490

Middle Eastern (MID)

AF:

0.000484

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

0.000146

AC:

123

AN:

841686

Other (OTH)

AF:

0.000261

AC:

AN:

46047

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

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:

0.000109

AC:

AN:

110186

Hom.:

Cov.:

AF XY:

0.0000925

AC XY:

AN XY:

32416

show subpopulations

African (AFR)

AF:

0.000132

AC:

AN:

30272

American (AMR)

AF:

0.00

AC:

AN:

10223

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2633

East Asian (EAS)

AF:

0.00

AC:

AN:

3511

South Asian (SAS)

AF:

0.00

AC:

AN:

2553

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5734

Middle Eastern (MID)

AF:

0.00

AC:

AN:

235

European-Non Finnish (NFE)

AF:

0.000151

AC:

AN:

52868

Other (OTH)

AF:

0.00

AC:

AN:

1473

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.547

Heterozygous variant carriers

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:

0.000204

Hom.:

Bravo

AF:

0.000121

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.080

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.15

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.0089

FATHMM_MKL

Benign

0.0038

LIST_S2

Benign

0.60

M_CAP

Benign

0.0014

MetaRNN

Benign

0.044

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.74

PhyloP100

-0.66

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.1

REVEL

Benign

0.037

Sift

Benign

0.24

Sift4G

Benign

0.32

Polyphen

0.0080

Vest4

0.040

MVP

0.27

MPC

0.016

ClinPred

0.013

GERP RS

-1.4

Varity_R

0.029

gMVP

0.042

Mutation Taster

=100/0

polymorphism

(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