9-5762544-CGT-TGC

Variant names:

• chr9-5762544-CGT-TGC
• NM_020829.4:c.1996_1998delCGTinsTGC
• RIC1 p.Arg666Cys

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_020829.4(RIC1):​c.1996_1998delCGTinsTGC​(p.Arg666Cys) variant causes a missense change involving the alteration of a 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RIC1 NM_020829.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.74
• Publications: 0 publications found

Genes affected

RIC1 (HGNC:17686): (RIC1 homolog, RAB6A GEF complex partner 1) Enables guanyl-nucleotide exchange factor activity and small GTPase binding activity. Involved in several processes, including positive regulation of GTPase activity; regulation of extracellular matrix constituent secretion; and retrograde transport, endosome to Golgi. Located in cytosol and membrane. Part of Ric1-Rgp1 guanyl-nucleotide exchange factor complex. [provided by Alliance of Genome Resources, Apr 2022]

ERMP1 (HGNC:23703): (endoplasmic reticulum metallopeptidase 1) Predicted to enable metal ion binding activity and metalloexopeptidase activity. Involved in cellular response to oxidative stress. Acts upstream of or within endoplasmic reticulum unfolded protein response. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020829.4. 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
	RIC1	NM_020829.4	MANE Select	c.1996_1998delCGTinsTGC	p.Arg666Cys	missense	N/A	NP_065880.2	Q4ADV7-1
	RIC1	NM_001206557.2		c.1885_1887delCGTinsTGC	p.Arg629Cys	missense	N/A	NP_001193486.1	Q4ADV7-3
	RIC1	NM_001135920.4		c.1996_1998delCGTinsTGC	p.Arg666Cys	missense	N/A	NP_001129392.2	Q4ADV7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIC1	ENST00000414202.7	TSL:5 MANE Select	c.1996_1998delCGTinsTGC	p.Arg666Cys	missense	N/A	ENSP00000416696.2	Q4ADV7-1
	RIC1	ENST00000545641.5	TSL:1	c.1669_1671delCGTinsTGC	p.Arg557Cys	missense	N/A	ENSP00000439488.1	H0YFN7
	RIC1	ENST00000251879.10	TSL:1	c.1996_1998delCGTinsTGC	p.Arg666Cys	missense	N/A	ENSP00000251879.6	Q4ADV7-2

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		7.7

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: chr9-5762544;