17-58363580-TCG-ACC

Variant names:

• chr17-58363580-TCG-ACC
• NM_017763.6:c.394_396delCGAinsGGT
• RNF43 p.Arg132Gly

Variant summary

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

The NM_017763.6(RNF43):​c.394_396delCGAinsGGT​(p.Arg132Gly) variant causes a missense 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R132Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RNF43 NM_017763.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.22
• Publications: 0 publications found

Genes affected

RNF43 (HGNC:18505): (ring finger protein 43) The protein encoded by this gene is a RING-type E3 ubiquitin ligase and is predicted to contain a transmembrane domain, a protease-associated domain, an ectodomain, and a cytoplasmic RING domain. This protein is thought to negatively regulate Wnt signaling, and expression of this gene results in an increase in ubiquitination of frizzled receptors, an alteration in their subcellular distribution, resulting in reduced surface levels of these receptors. Mutations in this gene have been reported in multiple tumor cells, including colorectal and endometrial cancers. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2015]

ENSG00000285897 (HGNC:):

TSPOAP1-AS1 (HGNC:44148): (TSPOAP1, SUPT4H1 and RNF43 antisense RNA 1)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017763.6. 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
	RNF43	NM_017763.6	MANE Select	c.394_396delCGAinsGGT	p.Arg132Gly	missense	N/A	NP_060233.3
	RNF43	NM_001438820.1		c.394_396delCGAinsGGT	p.Arg132Gly	missense	N/A	NP_001425749.1
	RNF43	NM_001438821.1		c.394_396delCGAinsGGT	p.Arg132Gly	missense	N/A	NP_001425750.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF43	ENST00000407977.7	TSL:2 MANE Select	c.394_396delCGAinsGGT	p.Arg132Gly	missense	N/A	ENSP00000385328.2	Q68DV7-1
	RNF43	ENST00000577716.5	TSL:1	c.394_396delCGAinsGGT	p.Arg132Gly	missense	N/A	ENSP00000462764.1	Q68DV7-1
	RNF43	ENST00000584437.5	TSL:1	c.394_396delCGAinsGGT	p.Arg132Gly	missense	N/A	ENSP00000463069.1	Q68DV7-1

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		4.2

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: chr17-56440941;