rs587776875

Positions:

• chr10-27533747-CAAG-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP5

The NM_021252.5(RAB18):​c.277_279delAGA​(p.Arg93del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAB18 NM_021252.5 conservative_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 3.39

Genes affected

RAB18 (HGNC:14244): (RAB18, member RAS oncogene family) The protein encoded by this gene is a member of a family of Ras-related small GTPases that regulate membrane trafficking in organelles and transport vesicles. Knockdown studies is zebrafish suggest that this protein may have a role in eye and brain development. Mutations in this gene are associated with Warburg micro syndrome type 3. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

RAB18 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_021252.5. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 10-27533747-CAAG-C is Pathogenic according to our data. Variant chr10-27533747-CAAG-C is described in ClinVar as [Pathogenic]. Clinvar id is 30249.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr10-27533747-CAAG-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB18	NM_021252.5	c.277_279delAGA	p.Arg93del	conservative_inframe_deletion	5/7	ENST00000356940.11	NP_067075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB18	ENST00000356940.11	c.277_279delAGA	p.Arg93del	conservative_inframe_deletion	5/7	1	NM_021252.5	ENSP00000349415.7

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

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Warburg micro syndrome 3 Pathogenic:1 Other:1

Pathogenic, no assertion criteria provided	literature only	OMIM	Apr 08, 2011	- -
not provided, no classification provided	literature only	GeneReviews	-	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs587776875; hg19: chr10-27822676;