Genetic Variant SSX3:p.Phe108Leu (chrX-48352108-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021014.4(SSX3):c.322T>C(p.Phe108Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,095,949 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F108Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )

Consequence

SSX3
NM_021014.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.19

Publications

0 publications found

Variant links:

Genes affected

SSX3 (HGNC:11337): (SSX family member 3) 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. [provided by RefSeq, Jul 2013]

SSX3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06737819).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021014.4. 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
	SSX3	NM_021014.4	MANE Select	c.322T>C	p.Phe108Leu	missense	Exon 5 of 8	NP_066294.1	Q99909-1
	SSX3	NR_176964.1		n.412T>C		non_coding_transcript_exon	Exon 5 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SSX3	ENST00000298396.7	TSL:1 MANE Select	c.322T>C	p.Phe108Leu	missense	Exon 5 of 8	ENSP00000298396.2	Q99909-1
SSX3	ENST00000612497.1	TSL:5	c.322T>C	p.Phe108Leu	missense	Exon 4 of 5	ENSP00000480427.1	A0A087WWQ6
SSX3	ENST00000376893.7	TSL:2	c.322T>C	p.Phe108Leu	missense	Exon 5 of 8	ENSP00000366090.3	Q99909-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000182

AC:

AN:

1095949

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

361669

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26361

American (AMR)

AF:

0.00

AC:

AN:

35185

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19352

East Asian (EAS)

AF:

0.00

AC:

AN:

30160

South Asian (SAS)

AF:

0.00

AC:

AN:

54090

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40471

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4064

European-Non Finnish (NFE)

AF:

0.00000238

AC:

AN:

840280

Other (OTH)

AF:

0.00

AC:

AN:

45986

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.062

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.021

FATHMM_MKL

Benign

0.00030

LIST_S2

Benign

0.55

M_CAP

Benign

0.0015

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

-1.2

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.5

REVEL

Benign

0.021

Sift

Benign

0.67

Sift4G

Benign

0.36

Polyphen

0.0

Vest4

0.12

MutPred

0.26

Gain of catalytic residue at F108 (P = 0.0971)

MVP

0.20

MPC

0.022

ClinPred

0.059

GERP RS

0.27

Varity_R

0.065

gMVP

0.043

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over