Variant X-103825520-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_016370.4(RAB9B):c.265G>A(p.Val89Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000281 in 1,209,958 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.000026 ( 0 hom. 8 hem. )

Consequence

RAB9B
NM_016370.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.11

Variant links:

Genes affected

RAB9B (HGNC:14090): (RAB9B, member RAS oncogene family) This gene encodes a member of a subfamily of RAS small guanosine triphosphate (GTP)-binding proteins that regulate membrane trafficking. The encoded protein may be involved in endosome-to-Golgi transport. [provided by RefSeq, Jan 2010]

RAB9B links:

ENSG00000288597 (HGNC:):

ENSG00000288597 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2493878).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB9B	NM_016370.4 link	c.265G>A	p.Val89Met	missense_variant	3/3	ENST00000243298.3	NP_057454.1	Q9NP90
RAB9B	NR_146558.2 link	n.198+6540G>A		intron_variant
RAB9B	NR_146560.2 link	n.198+6540G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB9B	ENST00000243298.3 link	c.265G>A	p.Val89Met	missense_variant	3/3	1	NM_016370.4	ENSP00000243298.2		Q9NP90

Frequencies

GnomAD3 genomes

AF:

0.0000448

AC:

AN:

111693

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

33853

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00140

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000104

AC:

AN:

182976

Hom.:

AF XY:

0.0000888

AC XY:

AN XY:

67542

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00137

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:

0.0000264

AC:

AN:

1098210

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

363570

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000828

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.0000447

AC:

AN:

111748

Hom.:

Cov.:

AF XY:

0.0000590

AC XY:

AN XY:

33918

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00140

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000680

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000988

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

Jan 09, 2023

The c.265G>A (p.V89M) alteration is located in exon 3 (coding exon 1) of the RAB9B gene. This alteration results from a G to A substitution at nucleotide position 265, causing the valine (V) at amino acid position 89 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

Uncertain

0.43

BayesDel_addAF

Uncertain

0.079

BayesDel_noAF

Pathogenic

0.31

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.25

MetaSVM

Uncertain

0.47

MutationAssessor

Uncertain

2.4

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.9

REVEL

Pathogenic

0.77

Sift

Uncertain

0.011

Sift4G

Uncertain

0.011

Polyphen

0.99

Vest4

0.58

MutPred

0.78

Loss of catalytic residue at V89 (P = 0.0243);

MVP

0.98

MPC

1.7

ClinPred

0.19

GERP RS

5.8

Varity_R

0.73

gMVP

0.88

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