10-27509751-G-T

Variant names:

• chr10-27509751-G-T
• rs188397633
• NM_021252.5:c.69-124G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021252.5(RAB18):​c.69-124G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RAB18 NM_021252.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.679
• 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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB18	NM_021252.5	c.69-124G>T		intron_variant	Intron 1 of 6	ENST00000356940.11	NP_067075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB18	ENST00000356940.11	c.69-124G>T		intron_variant	Intron 1 of 6	1	NM_021252.5	ENSP00000349415.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 635678 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 341498

African (AFR) AF: 0.00 AC: 0 AN: 17530

American (AMR) AF: 0.00 AC: 0 AN: 35968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20538

East Asian (EAS) AF: 0.00 AC: 0 AN: 33574

South Asian (SAS) AF: 0.00 AC: 0 AN: 65566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2596

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 389666

Other (OTH) AF: 0.00 AC: 0 AN: 33032

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.1
DANN	Benign	0.40
PhyloP100		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs188397633; hg19: chr10-27798680;