15-63263560-G-A

Position:

• chr15-63263560-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000321437.9(RAB8B):​c.565G>A​(p.Val189Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAB8B ENST00000321437.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.55

Genes affected

RAB8B (HGNC:30273): (RAB8B, member RAS oncogene family) RAB proteins, like RAB8B, are low molecular mass monomeric GTPases that localize on the cytoplasmic surfaces of distinct membrane-bound organelles. RAB proteins function in intracellular vesicle transport by aiding in the docking and/or fusion of vesicles with their target membranes (summary by Chen et al., 1997 [PubMed 9030196]).[supplied by OMIM, Nov 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22316629).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB8B	NM_016530.3	c.565G>A	p.Val189Met	missense_variant	8/8	ENST00000321437.9	NP_057614.1
RAB8B	XM_017022312.1	c.322G>A	p.Val108Met	missense_variant	9/9		XP_016877801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB8B	ENST00000321437.9	c.565G>A	p.Val189Met	missense_variant	8/8	1	NM_016530.3	ENSP00000312734.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 30, 2024

The c.565G>A (p.V189M) alteration is located in exon 8 (coding exon 8) of the RAB8B gene. This alteration results from a G to A substitution at nucleotide position 565, causing the valine (V) at amino acid position 189 to be replaced by a methionine (M). 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	Benign	0.28
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.091	T
Eigen	Benign	0.021
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.18
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.035	D
Polyphen		0.032	B
Vest4		0.35
MutPred		0.31		Loss of methylation at K190 (P = 0.0312);
MVP		0.71
MPC		1.2
ClinPred		0.85	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-63555759;