rs782638761

Variant names:

Variant summary

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

The NM_021014.4(SSX3):c.283C>G(p.Gln95Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000053 in 1,206,929 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 25 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. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000056 ( 0 hom. 24 hem. )

Consequence

SSX3
NM_021014.4 missense, splice_region

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.283

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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03404978).

BP6

Variant X-48352147-G-C is Benign according to our data. Variant chrX-48352147-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3449933.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 24 gene

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.283C>G	p.Gln95Glu	missense splice_region	Exon 5 of 8	NP_066294.1	Q99909-1
	SSX3	NR_176964.1		n.373C>G		splice_region 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.283C>G	p.Gln95Glu	missense splice_region	Exon 5 of 8	ENSP00000298396.2	Q99909-1
SSX3	ENST00000612497.1	TSL:5	c.283C>G	p.Gln95Glu	missense splice_region	Exon 4 of 5	ENSP00000480427.1	A0A087WWQ6
SSX3	ENST00000376893.7	TSL:2	c.283C>G	p.Gln95Glu	missense splice_region	Exon 5 of 8	ENSP00000366090.3	Q99909-2

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112377

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000646

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000370

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000273

AC:

AN:

183270

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000367

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000557

AC:

AN:

1094499

Hom.:

Cov.:

AF XY:

0.0000666

AC XY:

AN XY:

360491

show subpopulations

African (AFR)

AF:

0.0000380

AC:

AN:

26336

American (AMR)

AF:

0.0000569

AC:

AN:

35177

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19338

East Asian (EAS)

AF:

0.00

AC:

AN:

30153

South Asian (SAS)

AF:

0.0000740

AC:

AN:

54060

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40465

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3796

European-Non Finnish (NFE)

AF:

0.0000620

AC:

AN:

839274

Other (OTH)

AF:

0.0000436

AC:

AN:

45900

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

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:

0.0000267

AC:

AN:

112430

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

34580

show subpopulations

African (AFR)

AF:

0.0000645

AC:

AN:

31017

American (AMR)

AF:

0.00

AC:

AN:

10586

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3566

South Asian (SAS)

AF:

0.000371

AC:

AN:

2693

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6146

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53323

Other (OTH)

AF:

0.00

AC:

AN:

1544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.000144

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000412

AC:

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

0.040

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.052

(source)

DANN

Benign

0.49

DEOGEN2

Benign

0.0019

FATHMM_MKL

Benign

0.000080

LIST_S2

Benign

0.42

M_CAP

Benign

0.00097

MetaRNN

Benign

0.034

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-2.6

PhyloP100

-0.28

PrimateAI

Benign

0.30

PROVEAN

Benign

1.9

REVEL

Benign

0.026

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.040

MutPred

0.35

Gain of relative solvent accessibility (P = 0.0275)

MVP

0.11

MPC

0.022

ClinPred

0.051

GERP RS

0.28

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.044

gMVP

0.016

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