3-141738375-GCC-CCG

Variant names:

• chr3-141738375-GCC-CCG
• NM_014245.5:c.34_36delGCCinsCCG
• RNF7 p.Ala12Pro

Variant summary

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

The NM_014245.5(RNF7):​c.34_36delGCCinsCCG​(p.Ala12Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. A12T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RNF7 NM_014245.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74
• Publications: 0 publications found

Genes affected

RNF7 (HGNC:10070): (ring finger protein 7) The protein encoded by this gene is a highly conserved ring finger protein. It is an essential subunit of SKP1-cullin/CDC53-F box protein ubiquitin ligases, which are a part of the protein degradation machinery important for cell cycle progression and signal transduction. This protein interacts with, and is a substrate of, casein kinase II (CSNK2A1/CKII). The phosphorylation of this protein by CSNK2A1 has been shown to promote the degradation of IkappaBalpha (CHUK/IKK-alpha/IKBKA) and p27Kip1(CDKN1B). Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ENSG00000285558 (HGNC:):

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014245.5. 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
	RNF7	NM_014245.5	MANE Select	c.34_36delGCCinsCCG	p.Ala12Pro	missense	N/A	NP_055060.1	Q9UBF6-1
	RNF7	NM_001201370.2		c.34_36delGCCinsCCG	p.Ala12Pro	missense	N/A	NP_001188299.1	Q9UBF6-4
	RNF7	NM_183237.3		c.34_36delGCCinsCCG	p.Ala12Pro	missense	N/A	NP_899060.1	Q9UBF6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF7	ENST00000273480.4	TSL:1 MANE Select	c.34_36delGCCinsCCG	p.Ala12Pro	missense	N/A	ENSP00000273480.3	Q9UBF6-1
	RNF7	ENST00000477012.5	TSL:1	n.34_36delGCCinsCCG		non_coding_transcript_exon	Exon 1 of 4	ENSP00000419339.1	Q9UBF6-2
	RNF7	ENST00000480908.1	TSL:4	c.34_36delGCCinsCCG	p.Ala12Pro	missense	N/A	ENSP00000419084.1	Q9UBF6-4

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		2.7

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: chr3-141457217;