chr3-42590917-C-T

Variant names:

• chr3-42590917-C-T
• rs1704802109
• NM_001370300.1:c.20C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001370300.1(SS18L2):​c.20C>T​(p.Pro7Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000135 in 1,262,872 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.31
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370300.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SS18L2	NM_001370300.1	MANE Select	c.20C>T	p.Pro7Leu	missense	Exon 1 of 3	NP_001357229.1	Q9UHA2
	SS18L2	NM_016305.4		c.20C>T	p.Pro7Leu	missense	Exon 2 of 4	NP_057389.1	Q9UHA2
	SEC22C	NM_001201572.2		c.-28+10043G>A		intron	N/A	NP_001188501.1	Q9BRL7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SS18L2	ENST00000011691.6	TSL:1 MANE Select	c.20C>T	p.Pro7Leu	missense	Exon 1 of 3	ENSP00000011691.4	Q9UHA2
	SS18L2	ENST00000447630.5	TSL:2	c.20C>T	p.Pro7Leu	missense	Exon 2 of 4	ENSP00000401115.1	Q9UHA2
	SS18L2	ENST00000897957.1		c.20C>T	p.Pro7Leu	missense	Exon 1 of 3	ENSP00000568016.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000135 AC: 17 AN: 1262872 Hom.: 0 Cov.: 34 AF XY: 0.0000192 AC XY: 12 AN XY: 626060

African (AFR) AF: 0.00 AC: 0 AN: 27778

American (AMR) AF: 0.00 AC: 0 AN: 38606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18570

East Asian (EAS) AF: 0.00 AC: 0 AN: 21030

South Asian (SAS) AF: 0.00 AC: 0 AN: 84464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37060

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4676

European-Non Finnish (NFE) AF: 0.0000173 AC: 17 AN: 983656

Other (OTH) AF: 0.00 AC: 0 AN: 47032

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.85	T
PhyloP100		4.3
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.087	B
Vest4		0.69
MutPred		0.49		Gain of sheet (P = 0.0266)
MVP		0.15
MPC		0.46
ClinPred		0.99	D
GERP RS		6.0
PromoterAI		-0.10	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.47
gMVP		0.78
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs1704802109; hg19: chr3-42632409;