Variant 15-63263577-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_016530.3(RAB8B):c.582C>A(p.Asn194Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

RAB8B
NM_016530.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.165

Variant links:

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]

RAB8B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06741187).

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB8B	NM_016530.3 linkuse as main transcript	c.582C>A	p.Asn194Lys	missense_variant	8/8	ENST00000321437.9	NP_057614.1
RAB8B	XM_017022312.1 linkuse as main transcript	c.339C>A	p.Asn113Lys	missense_variant	9/9		XP_016877801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RAB8B	ENST00000321437.9 linkuse as main transcript	c.582C>A	p.Asn194Lys	missense_variant	8/8	1	NM_016530.3	ENSP00000312734	P1
RAB8B	ENST00000558119.5 linkuse as main transcript	c.*362C>A		3_prime_UTR_variant, NMD_transcript_variant	9/9	2		ENSP00000453679
RAB8B	ENST00000559927.1 linkuse as main transcript	c.*567C>A		3_prime_UTR_variant, NMD_transcript_variant	9/9	5		ENSP00000453111

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251380

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1460778

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726774

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 21, 2024

The c.582C>A (p.N194K) alteration is located in exon 8 (coding exon 8) of the RAB8B gene. This alteration results from a C to A substitution at nucleotide position 582, causing the asparagine (N) at amino acid position 194 to be replaced by a lysine (K). 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

0.18

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.059

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.82

M_CAP

Benign

0.0083

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.41

MutationTaster

Benign

0.99

N;N

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.18

REVEL

Benign

0.080

Sift

Benign

0.82

Sift4G

Benign

0.41

Polyphen

0.0

Vest4

0.17

MutPred

0.25

Gain of methylation at N194 (P = 0.0329);

MVP

0.68

MPC

1.1

ClinPred

0.062

GERP RS

2.6

Varity_R

0.034

gMVP

0.40

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over