Variant 17-82657916-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006822.3(RAB40B):c.784C>A(p.Pro262Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,291,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

RAB40B
NM_006822.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65

Variant links:

Genes affected

RAB40B (HGNC:18284): (RAB40B, member RAS oncogene family) The protein encoded by this gene has similarity to a yeast protein which suggests a role of the gene product in regulating secretory vesicles. [provided by RefSeq, Jul 2008]

RAB40B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.09138024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB40B	NM_006822.3 linkuse as main transcript	c.784C>A	p.Pro262Thr	missense_variant	6/6	ENST00000571995.6	NP_006813.1	Q12829
RAB40B	XM_011523528.3 linkuse as main transcript	c.733C>A	p.Pro245Thr	missense_variant	6/6		XP_011521830.1
RAB40B	XM_006722271.4 linkuse as main transcript	c.664C>A	p.Pro222Thr	missense_variant	6/6		XP_006722334.1
RAB40B	XM_017024042.2 linkuse as main transcript	c.604C>A	p.Pro202Thr	missense_variant	6/6		XP_016879531.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB40B	ENST00000571995.6 linkuse as main transcript	c.784C>A	p.Pro262Thr	missense_variant	6/6	1	NM_006822.3	ENSP00000461785.1		Q12829

Frequencies

GnomAD3 genomes

AF:

0.0000203

AC:

AN:

147528

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000493

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251406

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000962

AC:

AN:

1144026

Hom.:

Cov.:

AF XY:

0.0000104

AC XY:

AN XY:

579016

show subpopulations

Gnomad4 AFR exome

AF:

0.000194

Gnomad4 AMR exome

AF:

0.0000950

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000236

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000203

AC:

AN:

147528

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

71952

show subpopulations

Gnomad4 AFR

AF:

0.0000493

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000150

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

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

Nov 05, 2021

The c.784C>A (p.P262T) alteration is located in exon 6 (coding exon 6) of the RAB40B gene. This alteration results from a C to A substitution at nucleotide position 784, causing the proline (P) at amino acid position 262 to be replaced by a threonine (T). 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

0.075

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.36

CADD

Benign

9.3

DANN

Benign

0.86

DEOGEN2

Benign

0.011

T;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.091

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.

PrimateAI

Benign

0.25

REVEL

Benign

0.045

Sift4G

Benign

0.31

T;T

Polyphen

0.0

B;.

Vest4

0.083

MutPred

0.23

Loss of catalytic residue at P262 (P = 0.0081);.;

MVP

0.90

MPC

0.45

ClinPred

0.020

GERP RS

0.10

Varity_R

0.059

gMVP

0.53

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