14-92652329-GG-AA

Variant names:

• chr14-92652329-GG-AA
• NM_024832.5:c.1280_1281delGGinsAA
• RIN3 p.Arg427Gln

Variant summary

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

The NM_024832.5(RIN3):​c.1280_1281delGGinsAA​(p.Arg427Gln) 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. R427W) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RIN3 NM_024832.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 0 publications found

Genes affected

RIN3 (HGNC:18751): (Ras and Rab interactor 3) Summary: This protein encoded by this gene is a member of the RIN family of Ras interaction-interference proteins, which are binding partners to the RAB5 small GTPases. The protein functions as a guanine nucleotide exchange for RAB5B and RAB31. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024832.5. 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
	RIN3	NM_024832.5	MANE Select	c.1280_1281delGGinsAA	p.Arg427Gln	missense	N/A	NP_079108.3
	RIN3	NM_001319987.2		c.1055_1056delGGinsAA	p.Arg352Gln	missense	N/A	NP_001306916.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIN3	ENST00000216487.12	TSL:1 MANE Select	c.1280_1281delGGinsAA	p.Arg427Gln	missense	N/A	ENSP00000216487.7	Q8TB24-1
	RIN3	ENST00000555589.5	TSL:1	n.*727_*728delGGinsAA		non_coding_transcript_exon	Exon 5 of 9	ENSP00000450682.1	G3V2I7
	RIN3	ENST00000555589.5	TSL:1	n.*727_*728delGGinsAA		3_prime_UTR	Exon 5 of 9	ENSP00000450682.1	G3V2I7

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.16

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: chr14-93118674;