3-42590911-T-A

Variant names:

• chr3-42590911-T-A
• NM_001370300.1:c.14T>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001370300.1(SS18L2):​c.14T>A​(p.Phe5Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SS18L2 NM_001370300.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.37

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.87

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SS18L2	NM_001370300.1	c.14T>A	p.Phe5Tyr	missense_variant	Exon 1 of 3	ENST00000011691.6	NP_001357229.1
SS18L2	NM_016305.4	c.14T>A	p.Phe5Tyr	missense_variant	Exon 2 of 4		NP_057389.1
SEC22C	NM_001201572.2	c.-28+10049A>T		intron_variant	Intron 1 of 6		NP_001188501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SS18L2	ENST00000011691.6	c.14T>A	p.Phe5Tyr	missense_variant	Exon 1 of 3	1	NM_001370300.1	ENSP00000011691.4
SS18L2	ENST00000447630.5	c.14T>A	p.Phe5Tyr	missense_variant	Exon 2 of 4	2		ENSP00000401115.1
SEC22C	ENST00000417572.5	c.-28+10049A>T		intron_variant	Intron 1 of 6	3		ENSP00000407564.1
SEC22C	ENST00000450981.5	c.-179-3349A>T		intron_variant	Intron 1 of 4	3		ENSP00000397170.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.14T>A (p.F5Y) alteration is located in exon 1 (coding exon 1) of the SS18L2 gene. This alteration results from a T to A substitution at nucleotide position 14, causing the phenylalanine (F) at amino acid position 5 to be replaced by a tyrosine (Y). 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	0.49
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.049	T;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.47	.;T
M_CAP	Pathogenic	0.41	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Benign	-0.57	T
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.20
Sift	Uncertain	0.015	D;D
Sift4G	Uncertain	0.041	D;D
Polyphen		0.98	D;D
Vest4		0.59
MutPred		0.78		Loss of stability (P = 0.0274);Loss of stability (P = 0.0274);
MVP		0.14
MPC		1.2
ClinPred		0.99	D
GERP RS		6.0
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.52
gMVP		0.61

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: chr3-42632403;