X-48192251-A-G

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -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. 12/20 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

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

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

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSX5	NM_175723.2 link	c.311T>C	p.Leu104Pro	missense_variant	Exon 5 of 8	ENST00000347757.6	NP_783729.1	O60225-1
SSX5	NM_021015.4 link	c.434T>C	p.Leu145Pro	missense_variant	Exon 6 of 9		NP_066295.3	O60225-2
SSX5	XM_011543949.3 link	c.311T>C	p.Leu104Pro	missense_variant	Exon 5 of 8		XP_011542251.1	O60225-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SSX5	ENST00000347757.6 link	c.311T>C	p.Leu104Pro	missense_variant	Exon 5 of 8	5	NM_175723.2	ENSP00000290558.1	O60225-1
SSX5	ENST00000311798.5 link	c.434T>C	p.Leu145Pro	missense_variant	Exon 6 of 9	5		ENSP00000312415.1	O60225-2
SSX5	ENST00000403001.3 link	n.131T>C		non_coding_transcript_exon_variant	Exon 1 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.0000268

AC:

AN:

112097

Hom.:

Cov.:

AF XY:

0.0000584

AC XY:

AN XY:

34245

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

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

183289

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

67853

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 SAS 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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000852

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000268

AC:

AN:

112097

Hom.:

Cov.:

AF XY:

0.0000584

AC XY:

AN XY:

34245

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.0000947

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 29, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.434T>C (p.L145P) alteration is located in exon 6 (coding exon 5) of the SSX5 gene. This alteration results from a T to C substitution at nucleotide position 434, causing the leucine (L) at amino acid position 145 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.027

T;.;T;.

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.69

.;T;T;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.7

M;.;M;.

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-2.7

D;N;D;D

REVEL

Benign

0.081

Sift

Uncertain

0.018

D;T;D;D

Sift4G

Uncertain

0.040

D;D;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.13

MutPred

0.19

Loss of stability (P = 0.0743);.;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

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