NM_021014.4:c.266A>G

Variant names:

• chrX-48354013-T-C
• NM_021014.4:c.266A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_021014.4(SSX3):​c.266A>G​(p.Asn89Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000456 in 1,095,875 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000046 (0 hom. 2 hem.)
• Consequence: SSX3 NM_021014.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.399
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15858492).
• BS2: High Hemizygotes in GnomAdExome4 at 2 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.266A>G	p.Asn89Ser	missense	Exon 4 of 8	NP_066294.1	Q99909-1
	SSX3	NR_176964.1		n.356A>G		non_coding_transcript_exon	Exon 4 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSX3	ENST00000298396.7	TSL:1 MANE Select	c.266A>G	p.Asn89Ser	missense	Exon 4 of 8	ENSP00000298396.2	Q99909-1
	SSX3	ENST00000612497.1	TSL:5	c.266A>G	p.Asn89Ser	missense	Exon 3 of 5	ENSP00000480427.1	A0A087WWQ6
	SSX3	ENST00000376893.7	TSL:2	c.266A>G	p.Asn89Ser	missense	Exon 4 of 8	ENSP00000366090.3	Q99909-2

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 0.00000456 AC: 5 AN: 1095875 Hom.: 0 Cov.: 30 AF XY: 0.00000553 AC XY: 2 AN XY: 361457

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

African (AFR) AF: 0.00 AC: 0 AN: 26335

American (AMR) AF: 0.00 AC: 0 AN: 35187

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19347

East Asian (EAS) AF: 0.00 AC: 0 AN: 30164

South Asian (SAS) AF: 0.00 AC: 0 AN: 54104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40475

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4128

European-Non Finnish (NFE) AF: 0.00000595 AC: 5 AN: 840152

Other (OTH) AF: 0.00 AC: 0 AN: 45983

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000568638), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 21

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	8.7
DANN	Uncertain	0.97
DEOGEN2	Benign	0.030	T
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.00088	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-0.40
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.4	N
REVEL	Benign	0.022
Sift	Benign	0.23	T
Sift4G	Benign	0.076	T
Polyphen		0.90	P
Vest4		0.079
MutPred		0.27		Gain of loop (P = 0.0502)
MVP		0.13
MPC		0.040
ClinPred		0.44	T
GERP RS		-0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.053
gMVP		0.026
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chrX-48213448;