1-84650426-A-C

Position:

• chr1-84650426-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_001166293.2(SSX2IP):​c.1606T>G​(p.Ser536Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SSX2IP NM_001166293.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.69

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity ADIP_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18489796).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSX2IP	NM_001166293.2	c.1606T>G	p.Ser536Ala	missense_variant	13/14	ENST00000342203.8	NP_001159765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSX2IP	ENST00000342203.8	c.1606T>G	p.Ser536Ala	missense_variant	13/14	1	NM_001166293.2	ENSP00000340279.3
SSX2IP	ENST00000476905.6	n.*203T>G		non_coding_transcript_exon_variant	15/16	2		ENSP00000474925.1
SSX2IP	ENST00000476905.6	n.*203T>G		3_prime_UTR_variant	15/16	2		ENSP00000474925.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 17, 2023

The c.1606T>G (p.S536A) alteration is located in exon 14 (coding exon 12) of the SSX2IP gene. This alteration results from a T to G substitution at nucleotide position 1606, causing the serine (S) at amino acid position 536 to be replaced by an alanine (A). 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	0.073
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	.;T;.;T
Eigen	Benign	-0.075
Eigen_PC	Benign	0.13
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.68	T;T;.;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	.;L;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.65	N;N;.;.
REVEL	Benign	0.036
Sift	Benign	0.13	T;T;.;.
Sift4G	Benign	0.65	T;T;T;D
Polyphen		0.026	.;B;.;.
Vest4		0.31
MutPred		0.19		.;Loss of phosphorylation at S536 (P = 0.0218);.;.;
MVP		0.63
MPC		0.068
ClinPred		0.55	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.081
gMVP		0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs1650049277; hg19: chr1-85116109;