Genetic Variant NM_173358.2:c.506G>A (chrX-52645504-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_173358.2(SSX7):c.506G>A(p.Arg169His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,201,515 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000093 ( 0 hom., 0 hem., cov: 20)

Exomes 𝑓: 0.000011 ( 0 hom. 4 hem. )

Consequence

SSX7
NM_173358.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.351

Publications

0 publications found

Variant links:

Genes affected

SSX7 (HGNC:19653): (SSX family member 7) 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 spontaneously humoral and cellular immune responses in cancer patients, and are potentially useful targets in cancer vaccine-based immunotherapy. SSX1, SSX2 and SSX4 genes have been involved in the t(X;18) translocation characteristically found in all synovial sarcomas. This gene appears not to be involved in this type of chromosome translocation. [provided by RefSeq, Jul 2008]

SSX7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30613035).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173358.2. 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
	SSX7	NM_173358.2	MANE Select	c.506G>A	p.Arg169His	missense	Exon 7 of 8	NP_775494.1	Q7RTT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSX7	ENST00000298181.6	TSL:5 MANE Select	c.506G>A	p.Arg169His	missense	Exon 7 of 8	ENSP00000298181.5	Q7RTT5

Frequencies

GnomAD3 genomes

AF:

0.00000931

AC:

AN:

107404

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000192

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1094111

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

360739

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26308

American (AMR)

AF:

0.00

AC:

AN:

35111

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19321

East Asian (EAS)

AF:

0.00

AC:

AN:

30169

South Asian (SAS)

AF:

0.00

AC:

AN:

53848

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40489

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

2881

European-Non Finnish (NFE)

AF:

0.0000119

AC:

AN:

840116

Other (OTH)

AF:

0.0000218

AC:

AN:

45868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

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:

0.00000931

AC:

AN:

107404

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

29790

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

29485

American (AMR)

AF:

0.00

AC:

AN:

9804

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2590

East Asian (EAS)

AF:

0.00

AC:

AN:

3439

South Asian (SAS)

AF:

0.00

AC:

AN:

2315

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5381

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.0000192

AC:

AN:

52060

Other (OTH)

AF:

0.00

AC:

AN:

1425

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.0000151

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

0.13

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.85

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.14

FATHMM_MKL

Benign

0.0026

LIST_S2

Benign

0.69

M_CAP

Benign

0.0011

MetaRNN

Benign

0.31

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PhyloP100

0.35

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.053

Sift

Uncertain

0.020

Sift4G

Uncertain

0.022

Polyphen

0.55

Vest4

0.20

MutPred

0.67

Loss of MoRF binding (P = 0.0525)

MVP

0.067

MPC

0.013

ClinPred

0.58

GERP RS

-1.1

Varity_R

0.19

gMVP

0.039

Mutation Taster

=95/5

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