Variant chr1-84650438-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001166293.2(SSX2IP):c.1594A>G(p.Lys532Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SSX2IP
NM_001166293.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.09

Variant links:

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]

SSX2IP links:

SSX2IP (HGNC:):

SSX2IP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19516268).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSX2IP	NM_001166293.2 linkuse as main transcript	c.1594A>G	p.Lys532Glu	missense_variant	13/14	ENST00000342203.8	NP_001159765.1	Q9Y2D8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SSX2IP	ENST00000342203.8 linkuse as main transcript	c.1594A>G	p.Lys532Glu	missense_variant	13/14	1	NM_001166293.2	ENSP00000340279.3	Q9Y2D8-1
SSX2IP	ENST00000476905.6 linkuse as main transcript	n.*191A>G		non_coding_transcript_exon_variant	15/16	2		ENSP00000474925.1	S4R403
SSX2IP	ENST00000476905.6 linkuse as main transcript	n.*191A>G		3_prime_UTR_variant	15/16	2		ENSP00000474925.1	S4R403

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2021

The c.1594A>G (p.K532E) alteration is located in exon 14 (coding exon 12) of the SSX2IP gene. This alteration results from a A to G substitution at nucleotide position 1594, causing the lysine (K) at amino acid position 532 to be replaced by a glutamic acid (E). 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

0.090

BayesDel_addAF

Benign

-0.026

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.052

.;T;.;T

Eigen

Benign

-0.0089

Eigen_PC

Benign

0.041

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

T;T;.;T

M_CAP

Benign

0.0085

MetaRNN

Benign

0.20

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

.;L;.;.

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.78

N;N;.;.

REVEL

Benign

0.14

Sift

Uncertain

0.014

D;D;.;.

Sift4G

Benign

0.074

T;T;T;D

Polyphen

0.92

.;P;.;.

Vest4

0.45

MutPred

0.25

.;Loss of helix (P = 0.0068);.;.;

MVP

0.63

MPC

0.12

ClinPred

0.57

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.35

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over