rs1704802109

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-42590917-C-G
• chr3-42590917-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001370300.1(SS18L2):​c.20C>G​(p.Pro7Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000317 in 1,262,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P7L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: SS18L2 NM_001370300.1 missense
• Clinical Significance: Not reported in ClinVar
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.792

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>G	p.Pro7Arg	missense	Exon 1 of 3	NP_001357229.1	Q9UHA2
	SS18L2	NM_016305.4		c.20C>G	p.Pro7Arg	missense	Exon 2 of 4	NP_057389.1	Q9UHA2
	SEC22C	NM_001201572.2		c.-28+10043G>C		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>G	p.Pro7Arg	missense	Exon 1 of 3	ENSP00000011691.4	Q9UHA2
	SS18L2	ENST00000447630.5	TSL:2	c.20C>G	p.Pro7Arg	missense	Exon 2 of 4	ENSP00000401115.1	Q9UHA2
	SS18L2	ENST00000897957.1		c.20C>G	p.Pro7Arg	missense	Exon 1 of 3	ENSP00000568016.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000317 AC: 4 AN: 1262872 Hom.: 0 Cov.: 34 AF XY: 0.00000479 AC XY: 3 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: 0.000190 AC: 4 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: 0.00 AC: 0 AN: 983656

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.43	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.29	T
PhyloP100		4.3
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.27
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.98	D
Vest4		0.79
MutPred		0.44		Gain of MoRF binding (P = 0)
MVP		0.23
MPC		1.2
ClinPred		0.98	D
GERP RS		6.0
PromoterAI		-0.015	Neutral
Varity_R		0.48
gMVP		0.77
Mutation Taster		=69/31	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;