Genetic Variant NM_021014.4:c.448A>G (chrX-48350005-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021014.4(SSX3):c.448A>G(p.Lys150Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,206 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: not found (cov: 22)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

SSX3
NM_021014.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.64

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13459238).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSX3	NM_021014.4 link	c.448A>G	p.Lys150Glu	missense_variant	Exon 6 of 8	ENST00000298396.7	NP_066294.1	Q99909-1
SSX3	XM_011543885.3 link	c.448A>G	p.Lys150Glu	missense_variant	Exon 6 of 7		XP_011542187.1	Q99909-2A0A024R1B1
SSX3	NR_176964.1 link	n.538A>G		non_coding_transcript_exon_variant	Exon 6 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SSX3	ENST00000298396.7 link	c.448A>G	p.Lys150Glu	missense_variant	Exon 6 of 8	1	NM_021014.4	ENSP00000298396.2	Q99909-1
SSX3	ENST00000612497.1 link	c.448A>G	p.Lys150Glu	missense_variant	Exon 5 of 5	5		ENSP00000480427.1	A0A087WWQ6
SSX3	ENST00000376893.7 link	c.448A>G	p.Lys150Glu	missense_variant	Exon 6 of 8	2		ENSP00000366090.3	Q99909-2
SSX3	ENST00000376895.2 link	n.266A>G		non_coding_transcript_exon_variant	Exon 2 of 4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1098206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363566

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.448A>G (p.K150E) alteration is located in exon 6 (coding exon 5) of the SSX3 gene. This alteration results from a A to G substitution at nucleotide position 448, causing the lysine (K) at amino acid position 150 to be replaced by a glutamic acid (E). 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

0.10

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.90

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.019

T;.;.

FATHMM_MKL

Benign

0.0037

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.0040

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.5

M;M;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-2.2

N;N;.

REVEL

Benign

0.028

Sift

Benign

0.095

T;D;.

Sift4G

Uncertain

0.016

D;D;D

Polyphen

0.91

P;.;.

Vest4

0.068

MutPred

0.37

Loss of methylation at K150 (P = 0.008);Loss of methylation at K150 (P = 0.008);Loss of methylation at K150 (P = 0.008);

MVP

0.19

MPC

0.071

ClinPred

1.0

GERP RS

-1.0

Varity_R

0.13

gMVP

0.052

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over