Variant 3-42590932-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001370300.1(SS18L2):c.35G>C(p.Gly12Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,305,762 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

SS18L2
NM_001370300.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.58

Variant links:

Genes affected

SS18L2 (HGNC:15593): (SS18 like 2) Synovial sarcomas occur most frequently in the extremities around large joints. More than 90% of cases have a recurrent and specific chromosomal translocation, t(X;18)(p11.2;q11.2), in which the 5-prime end of the SS18 gene (MIM 600192) is fused in-frame to the 3-prime end of the SSX1 (MIM 312820), SSX2 (MIM 300192), or SSX4 (MIM 300326) gene. The SS18L2 gene is homologous to SS18.[supplied by OMIM, Jul 2002]

SS18L2 links:

SEC22C (HGNC:16828): (SEC22 homolog C, vesicle trafficking protein) This gene encodes a member of the SEC22 family of vesicle trafficking proteins. The encoded protein is localized to the endoplasmic reticulum and may play a role in the early stages of ER-Golgi protein trafficking. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

SEC22C links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SS18L2	NM_001370300.1 linkuse as main transcript	c.35G>C	p.Gly12Ala	missense_variant	1/3	ENST00000011691.6	NP_001357229.1
SS18L2	NM_016305.4 linkuse as main transcript	c.35G>C	p.Gly12Ala	missense_variant	2/4		NP_057389.1	Q9UHA2A0A024R2Q8
SEC22C	NM_001201572.2 linkuse as main transcript	c.-28+10028C>G		intron_variant			NP_001188501.1	Q9BRL7-2A0A024R2Q1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SS18L2	ENST00000011691.6 linkuse as main transcript	c.35G>C	p.Gly12Ala	missense_variant	1/3	1	NM_001370300.1	ENSP00000011691.4	Q9UHA2
SS18L2	ENST00000447630.5 linkuse as main transcript	c.35G>C	p.Gly12Ala	missense_variant	2/4	2		ENSP00000401115.1	Q9UHA2
SEC22C	ENST00000417572.5 linkuse as main transcript	c.-28+10028C>G		intron_variant		3		ENSP00000407564.1	Q9BRL7-2
SEC22C	ENST00000450981.5 linkuse as main transcript	c.-179-3370C>G		intron_variant		3		ENSP00000397170.1	C9J2R1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250608

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135558

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1305762

Hom.:

Cov.:

AF XY:

0.0000123

AC XY:

AN XY:

648380

show subpopulations

Gnomad4 AFR exome

AF:

0.0000344

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:

0.0000138

Gnomad4 OTH exome

AF:

0.0000399

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000517

Hom.:

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

Jan 17, 2024

The c.35G>C (p.G12A) alteration is located in exon 1 (coding exon 1) of the SS18L2 gene. This alteration results from a G to C substitution at nucleotide position 35, causing the glycine (G) at amino acid position 12 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

0.29

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.77

.;T

M_CAP

Uncertain

0.21

MetaRNN

Uncertain

0.67

D;D

MetaSVM

Uncertain

-0.27

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-4.2

D;D

REVEL

Uncertain

0.35

Sift

Benign

0.050

D;D

Sift4G

Benign

0.20

T;T

Polyphen

1.0

D;D

Vest4

0.52

MutPred

0.69

Loss of loop (P = 0.0603);Loss of loop (P = 0.0603);

MVP

0.35

MPC

1.3

ClinPred

0.98

GERP RS

6.0

Varity_R

0.47

gMVP

0.60

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

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