1-84656457-T-C

Position:

• chr1-84656457-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001166293.2(SSX2IP):​c.1106A>G​(p.Asn369Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 0.641

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05713886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSX2IP	NM_001166293.2	c.1106A>G	p.Asn369Ser	missense_variant	10/14	ENST00000342203.8	NP_001159765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSX2IP	ENST00000342203.8	c.1106A>G	p.Asn369Ser	missense_variant	10/14	1	NM_001166293.2	ENSP00000340279.3
SSX2IP	ENST00000476905.6	n.1094A>G		non_coding_transcript_exon_variant	11/16	2		ENSP00000474925.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Nov 10, 2022

The c.1106A>G (p.N369S) alteration is located in exon 11 (coding exon 9) of the SSX2IP gene. This alteration results from a A to G substitution at nucleotide position 1106, causing the asparagine (N) at amino acid position 369 to be replaced by a serine (S). 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	0.059
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.1
DANN	Uncertain	0.98
DEOGEN2	Benign	0.050	.;T;.
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.77	T;T;.
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.057	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.95	.;L;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.4	N;N;.
REVEL	Benign	0.035
Sift	Benign	0.11	T;T;.
Sift4G	Benign	0.70	T;T;T
Polyphen		0.0020	.;B;.
Vest4		0.12
MutPred		0.17		.;Gain of phosphorylation at N369 (P = 0.0424);.;
MVP		0.24
MPC		0.056
ClinPred		0.085	T
GERP RS		2.0
Varity_R		0.029
gMVP		0.065

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: rs1651139952; hg19: chr1-85122140;