rs375917613

Variant names:

• chr1-84650383-C-A
• rs375917613
• NM_001166293.2:c.1649G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-84650383-C-A
• chr1-84650383-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001166293.2(SSX2IP):​c.1649G>T​(p.Arg550Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R550C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SSX2IP NM_001166293.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.978
• Publications: 0 publications found

Genes affected

SSX2IP (HGNC:16509): (SSX family member 2 interacting protein) This gene encodes a protein that binds the cancer-testis antigen Synovial Sarcoma X breakpoint 2 protein. The encoded protein may regulate the activity of Synovial Sarcoma X breakpoint 2 protein in malignant cells. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 3. [provided by RefSeq, Oct 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.077682674).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166293.2. 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
	SSX2IP	NM_001166293.2	MANE Select	c.1649G>T	p.Arg550Leu	missense	Exon 13 of 14	NP_001159765.1	Q9Y2D8-1
	SSX2IP	NM_001166417.2		c.1649G>T	p.Arg550Leu	missense	Exon 14 of 15	NP_001159889.1	Q9Y2D8-1
	SSX2IP	NM_014021.4		c.1649G>T	p.Arg550Leu	missense	Exon 14 of 15	NP_054740.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSX2IP	ENST00000342203.8	TSL:1 MANE Select	c.1649G>T	p.Arg550Leu	missense	Exon 13 of 14	ENSP00000340279.3	Q9Y2D8-1
	SSX2IP	ENST00000603677.1	TSL:1	c.206G>T	p.Arg69Leu	missense	Exon 3 of 3	ENSP00000473763.1	S4R2Y6
	SSX2IP	ENST00000476905.6	TSL:2	n.*246G>T		non_coding_transcript_exon	Exon 15 of 16	ENSP00000474925.1	S4R403

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.98
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.20
Sift	Benign	0.55	T
Sift4G	Benign	0.49	T
Polyphen		0.019	B
Vest4		0.28
MutPred		0.29		Gain of loop (P = 0.0166)
MVP		0.26
MPC		0.083
ClinPred		0.080	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.039
gMVP		0.15
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.20		Position offset: -21

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

Other links and lift over

dbSNP: rs375917613; hg19: chr1-85116066; COSMIC: COSV100642594; COSMIC: COSV100642594;