Genetic Variant RIC1:p.Ala39ValfsTer17 (chr9-5629420-G-GGCCGTGCT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020829.4(RIC1):c.115_116insTGCTGCCG(p.Ala39ValfsTer17) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,381,646 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

RIC1
NM_020829.4 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.00

Publications

0 publications found

Variant links:

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]

RIC1 Gene-Disease associations (from GenCC):

Catifa syndrome
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

RIC1 links:

ENSG00000286162 (HGNC:56906):

ENSG00000286162 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RIC1	NM_020829.4	MANE Select	c.115_116insTGCTGCCG	p.Ala39ValfsTer17	frameshift	Exon 1 of 26	NP_065880.2	Q4ADV7-1
RIC1	NM_001206557.2		c.115_116insTGCTGCCG	p.Ala39ValfsTer17	frameshift	Exon 1 of 25	NP_001193486.1	Q4ADV7-3
RIC1	NM_001135920.4		c.115_116insTGCTGCCG	p.Ala39ValfsTer17	frameshift	Exon 1 of 22	NP_001129392.2	Q4ADV7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RIC1	ENST00000414202.7	TSL:5 MANE Select	c.115_116insTGCTGCCG	p.Ala39ValfsTer17	frameshift	Exon 1 of 26	ENSP00000416696.2	Q4ADV7-1
RIC1	ENST00000251879.10	TSL:1	c.115_116insTGCTGCCG	p.Ala39ValfsTer17	frameshift	Exon 1 of 22	ENSP00000251879.6	Q4ADV7-2
RIC1	ENST00000894135.1		c.115_116insTGCTGCCG	p.Ala39ValfsTer17	frameshift	Exon 1 of 26	ENSP00000564194.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000152

AC:

AN:

131976

AF XY:

0.0000139

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000840

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000217

AC:

AN:

1381646

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

681796

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31410

American (AMR)

AF:

0.0000846

AC:

AN:

35462

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25118

East Asian (EAS)

AF:

0.00

AC:

AN:

35510

South Asian (SAS)

AF:

0.00

AC:

AN:

78836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33742

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078070

Other (OTH)

AF:

0.00

AC:

AN:

57812

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.0

Mutation Taster

=1/199

disease causing (fs/PTC)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over