chrX-48350005-T-C

Variant names:

• chrX-48350005-T-C
• NM_021014.4:c.448A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.64

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]

ACMG classification

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	c.448A>G	p.Lys150Glu	missense_variant	Exon 6 of 8	ENST00000298396.7	NP_066294.1
SSX3	XM_011543885.3	c.448A>G	p.Lys150Glu	missense_variant	Exon 6 of 7		XP_011542187.1
SSX3	NR_176964.1	n.538A>G		non_coding_transcript_exon_variant	Exon 6 of 9

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098206 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363566

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.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.019	T;.;.
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	M;M;.
PrimateAI	Benign	0.26	T
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	D
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.

Other links and lift over

hg19: chrX-48209440;