10-27504417-G-C

Variant names:

• chr10-27504417-G-C
• rs1007919312
• NM_021252.5:c.48G>C

Variant summary

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

The NM_021252.5(RAB18):​c.48G>C​(p.Glu16Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAB18 NM_021252.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.21
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Warburg micro syndrome 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Warburg micro syndrome

  Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet

LOC124902399 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB18	NM_021252.5	c.48G>C	p.Glu16Asp	missense_variant	Exon 1 of 7	ENST00000356940.11	NP_067075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB18	ENST00000356940.11	c.48G>C	p.Glu16Asp	missense_variant	Exon 1 of 7	1	NM_021252.5	ENSP00000349415.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Apr 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.48G>C (p.E16D) alteration is located in exon 1 (coding exon 1) of the RAB18 gene. This alteration results from a G to C substitution at nucleotide position 48, causing the glutamic acid (E) at amino acid position 16 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	23
DANN	Benign	0.91
DEOGEN2	Benign	0.18	.;.;T;T;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.89	D;D;D;D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.50	D;D;D;D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	-0.20	N;.;N;.;N
PhyloP100		4.2
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.2	N;.;N;N;.
REVEL	Benign	0.28
Sift	Benign	0.44	T;.;T;T;.
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0030	.;.;B;.;.
Vest4		0.65
MutPred		0.60		Loss of ubiquitination at K21 (P = 0.0699);Loss of ubiquitination at K21 (P = 0.0699);Loss of ubiquitination at K21 (P = 0.0699);Loss of ubiquitination at K21 (P = 0.0699);Loss of ubiquitination at K21 (P = 0.0699);
MVP		0.94
MPC		0.52
ClinPred		0.44	T
GERP RS		4.7
PromoterAI		-0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.85
Mutation Taster		=64/36	polymorphism

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

Other links and lift over

dbSNP: rs1007919312; hg19: chr10-27793346;