NM_001242908.2:c.724_726delCGCinsAGA

Variant names:

• chr1-37612821-GCG-TCT
• NM_001242908.2:c.724_726delCGCinsAGA
• RSPO1 p.243

Variant summary

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

The NM_001242908.2(RSPO1):​c.724_726delCGCinsAGA​(p.243) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R242R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RSPO1 NM_001242908.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67
• Publications: 0 publications found

Genes affected

RSPO1 (HGNC:21679): (R-spondin 1) This gene encodes a secreted activator protein with two cysteine-rich, furin-like domains and one thrombospondin type 1 domain. The encoded protein is a ligand for leucine-rich repeat-containing G-protein coupled receptors (LGR proteins) and positively regulates the Wnt signaling pathway. In mice, the protein induces the rapid onset of crypt cell proliferation and increases intestinal epithelial healing, providing a protective effect against chemotherapy-induced adverse effects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]

RSPO1 Gene-Disease associations (from GenCC):

• palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242908.2. 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
	RSPO1	NM_001242908.2	MANE Select	c.724_726delCGCinsAGA	p.243	synonymous	N/A	NP_001229837.1	Q2MKA7-1
	RSPO1	NM_001038633.4		c.724_726delCGCinsAGA	p.243	synonymous	N/A	NP_001033722.1	Q2MKA7-1
	RSPO1	NM_001242909.2		c.643_645delCGCinsAGA	p.216	synonymous	N/A	NP_001229838.1	Q2MKA7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPO1	ENST00000356545.7	TSL:1 MANE Select	c.724_726delCGCinsAGA	p.243	synonymous	N/A	ENSP00000348944.2	Q2MKA7-1
	RSPO1	ENST00000401068.1	TSL:1	c.724_726delCGCinsAGA	p.243	synonymous	N/A	ENSP00000383846.1	Q2MKA7-1
	RSPO1	ENST00000612451.4	TSL:1	c.535_537delCGCinsAGA	p.180	synonymous	N/A	ENSP00000479832.1	Q2MKA7-3

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-38078493;