rs761909429

Variant names:

• chr10-27504419-G-A
• rs761909429
• NM_021252.5:c.50G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-27504419-G-A
• chr10-27504419-G-C

Variant summary

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

The NM_021252.5(RAB18):​c.50G>A​(p.Ser17Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000706 in 1,416,972 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S17T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: RAB18 NM_021252.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.20
• 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.50G>A	p.Ser17Asn	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.50G>A	p.Ser17Asn	missense_variant	Exon 1 of 7	1	NM_021252.5	ENSP00000349415.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1416972 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 700052

African (AFR) AF: 0.00 AC: 0 AN: 32982

American (AMR) AF: 0.00 AC: 0 AN: 36606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25244

East Asian (EAS) AF: 0.00 AC: 0 AN: 38076

South Asian (SAS) AF: 0.00 AC: 0 AN: 80504

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 9.19e-7 AC: 1 AN: 1088722

Other (OTH) AF: 0.00 AC: 0 AN: 58826

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Benign	0.0084	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	.;.;D;T;.
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.94	D;D;D;D;D
M_CAP	Pathogenic	0.52	D
MetaRNN	Uncertain	0.68	D;D;D;D;D
MetaSVM	Uncertain	0.50	D
MutationAssessor	Uncertain	2.4	M;.;M;.;M
PhyloP100		4.2
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.5	D;.;D;D;.
REVEL	Uncertain	0.59
Sift	Uncertain	0.0040	D;.;D;D;.
Sift4G	Uncertain	0.0020	D;D;D;D;D
Polyphen		1.0	.;.;D;.;.
Vest4		0.63
MutPred		0.71		Loss of glycosylation at S17 (P = 0.0596);Loss of glycosylation at S17 (P = 0.0596);Loss of glycosylation at S17 (P = 0.0596);Loss of glycosylation at S17 (P = 0.0596);Loss of glycosylation at S17 (P = 0.0596);
MVP		0.77
MPC		1.1
ClinPred		0.97	D
GERP RS		4.6
PromoterAI		0.056	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.90
gMVP		0.85
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs761909429; hg19: chr10-27793348;