3-42591545-G-T

Variant summary

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

The NM_001370300.1(SS18L2):​c.90G>T​(p.Gln30His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SS18L2
NM_001370300.1 missense

Scores

9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.24
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]
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]

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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
SS18L2NM_001370300.1 linkuse as main transcriptc.90G>T p.Gln30His missense_variant 2/3 ENST00000011691.6 NP_001357229.1
SS18L2NM_016305.4 linkuse as main transcriptc.90G>T p.Gln30His missense_variant 3/4 NP_057389.1 Q9UHA2A0A024R2Q8
SEC22CNM_001201572.2 linkuse as main transcriptc.-28+9415C>A intron_variant NP_001188501.1 Q9BRL7-2A0A024R2Q1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SS18L2ENST00000011691.6 linkuse as main transcriptc.90G>T p.Gln30His missense_variant 2/31 NM_001370300.1 ENSP00000011691.4 Q9UHA2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsMay 11, 2022The c.90G>T (p.Q30H) alteration is located in exon 2 (coding exon 2) of the SS18L2 gene. This alteration results from a G to T substitution at nucleotide position 90, causing the glutamine (Q) at amino acid position 30 to be replaced by a histidine (H). 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
Uncertain
0.43
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.029
T;T
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.70
.;T
M_CAP
Benign
0.077
D
MetaRNN
Uncertain
0.64
D;D
MetaSVM
Benign
-0.69
T
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-0.74
N;N
REVEL
Benign
0.27
Sift
Benign
0.63
T;T
Sift4G
Benign
0.30
T;T
Polyphen
1.0
D;D
Vest4
0.70
MutPred
0.47
Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP
0.38
MPC
1.2
ClinPred
1.0
D
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.12
gMVP
0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-42633037; API