X-48350027-C-T

Variant names:

• chrX-48350027-C-T
• rs6651589
• NM_021014.4:c.426G>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_021014.4(SSX3):​c.426G>A​(p.Pro142Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,209,617 control chromosomes in the GnomAD database, including 29 homozygotes. There are 551 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0091 (12 hom., 263 hem., cov: 22)
  • Exomes 𝑓: 0.0010 (17 hom. 288 hem.)
• Consequence: SSX3 NM_021014.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.01

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 Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant X-48350027-C-T is Benign according to our data. Variant chrX-48350027-C-T is described in ClinVar as [Benign]. Clinvar id is 777792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.01 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00914 (1019/111430) while in subpopulation AFR AF= 0.0321 (986/30671). AF 95% confidence interval is 0.0305. There are 12 homozygotes in gnomad4. There are 263 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSX3	NM_021014.4	c.426G>A	p.Pro142Pro	synonymous_variant	Exon 6 of 8	ENST00000298396.7	NP_066294.1
SSX3	XM_011543885.3	c.426G>A	p.Pro142Pro	synonymous_variant	Exon 6 of 7		XP_011542187.1
SSX3	NR_176964.1	n.516G>A		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.426G>A	p.Pro142Pro	synonymous_variant	Exon 6 of 8	1	NM_021014.4	ENSP00000298396.2
SSX3	ENST00000612497.1	c.426G>A	p.Pro142Pro	synonymous_variant	Exon 5 of 5	5		ENSP00000480427.1
SSX3	ENST00000376893.7	c.426G>A	p.Pro142Pro	synonymous_variant	Exon 6 of 8	2		ENSP00000366090.3
SSX3	ENST00000376895.2	n.244G>A		non_coding_transcript_exon_variant	Exon 2 of 4	5

Frequencies

GnomAD3 genomes AF: 0.00915 AC: 1019 AN: 111377 Hom.: 12 Cov.: 22 AF XY: 0.00778 AC XY: 261 AN XY: 33559

Gnomad AFR AF: 0.0322

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00230

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000281

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000754

Gnomad OTH AF: 0.00333

GnomAD3 exomes AF: 0.00287 AC: 526 AN: 183366 Hom.: 10 AF XY: 0.00192 AC XY: 130 AN XY: 67800

Gnomad AFR exome AF: 0.0353

Gnomad AMR exome AF: 0.00153

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000157

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000122

Gnomad OTH exome AF: 0.00133

GnomAD4 exome AF: 0.00102 AC: 1122 AN: 1098187 Hom.: 17 Cov.: 32 AF XY: 0.000792 AC XY: 288 AN XY: 363547

Gnomad4 AFR exome AF: 0.0330

Gnomad4 AMR exome AF: 0.00193

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000662

Gnomad4 SAS exome AF: 0.000129

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000451

Gnomad4 OTH exome AF: 0.00295

GnomAD4 genome AF: 0.00914 AC: 1019 AN: 111430 Hom.: 12 Cov.: 22 AF XY: 0.00782 AC XY: 263 AN XY: 33622

Gnomad4 AFR AF: 0.0321

Gnomad4 AMR AF: 0.00220

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000282

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000754

Gnomad4 OTH AF: 0.00329

Alfa AF: 0.00359 Hom.: 10

Bravo AF: 0.0105

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.051
DANN	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6651589; hg19: chrX-48209462;