Genetic Variant SSX5:p.Leu104Pro (chrX-48192251-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_175723.2(SSX5):c.311T>C(p.Leu104Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000579 in 1,209,917 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.0000036 ( 0 hom. 2 hem. )

Consequence

SSX5
NM_175723.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.955

Publications

0 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10938758).

BS2

High Hemizygotes in GnomAd4 at 2 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.311T>C	p.Leu104Pro	missense	Exon 5 of 8	NP_783729.1	O60225-1
	SSX5	NM_021015.4		c.434T>C	p.Leu145Pro	missense	Exon 6 of 9	NP_066295.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SSX5	ENST00000347757.6	TSL:5 MANE Select	c.311T>C	p.Leu104Pro	missense	Exon 5 of 8	ENSP00000290558.1	O60225-1
SSX5	ENST00000311798.5	TSL:5	c.434T>C	p.Leu145Pro	missense	Exon 6 of 9	ENSP00000312415.1	O60225-2
SSX5	ENST00000403001.3	TSL:5	n.131T>C		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.0000268

AC:

AN:

112097

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000947

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000109

AC:

AN:

183289

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000729

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000364

AC:

AN:

1097820

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

363334

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26389

American (AMR)

AF:

0.0000852

AC:

AN:

35198

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19379

East Asian (EAS)

AF:

0.00

AC:

AN:

30198

South Asian (SAS)

AF:

0.00

AC:

AN:

54122

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4096

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841842

Other (OTH)

AF:

0.0000217

AC:

AN:

46066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.0000268

AC:

AN:

112097

Hom.:

Cov.:

AF XY:

0.0000584

AC XY:

AN XY:

34245

show subpopulations

African (AFR)

AF:

0.0000324

AC:

AN:

30825

American (AMR)

AF:

0.0000947

AC:

AN:

10565

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2650

East Asian (EAS)

AF:

0.00

AC:

AN:

3574

South Asian (SAS)

AF:

0.00

AC:

AN:

2669

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6127

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53260

Other (OTH)

AF:

0.00

AC:

AN:

1503

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.00

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.00000824

AC:

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

0.19

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.027

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.69

M_CAP

Benign

0.0048

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.7

PhyloP100

-0.95

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.081

Sift

Uncertain

0.018

Sift4G

Uncertain

0.040

Polyphen

1.0

Vest4

0.13

MutPred

0.19

Loss of stability (P = 0.0743)

MVP

0.36

MPC

0.13

ClinPred

0.43

GERP RS

-2.7

Varity_R

0.19

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over