Variant 17-82658618-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006822.3(RAB40B):c.438G>C(p.Glu146Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 1,613,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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: 33)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

RAB40B
NM_006822.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.61

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36525843).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB40B	NM_006822.3 linkuse as main transcript	c.438G>C	p.Glu146Asp	missense_variant	5/6	ENST00000571995.6	NP_006813.1	Q12829
RAB40B	XM_011523528.3 linkuse as main transcript	c.387G>C	p.Glu129Asp	missense_variant	5/6		XP_011521830.1
RAB40B	XM_006722271.4 linkuse as main transcript	c.318G>C	p.Glu106Asp	missense_variant	5/6		XP_006722334.1
RAB40B	XM_017024042.2 linkuse as main transcript	c.258G>C	p.Glu86Asp	missense_variant	5/6		XP_016879531.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB40B	ENST00000571995.6 linkuse as main transcript	c.438G>C	p.Glu146Asp	missense_variant	5/6	1	NM_006822.3	ENSP00000461785.1		Q12829

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152134

Hom.:

Cov.:

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250564

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135752

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000705

AC:

103

AN:

1461092

Hom.:

Cov.:

AF XY:

0.0000550

AC XY:

AN XY:

726874

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000917

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000294

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Dec 12, 2023

The c.438G>C (p.E146D) alteration is located in exon 5 (coding exon 5) of the RAB40B gene. This alteration results from a G to C substitution at nucleotide position 438, causing the glutamic acid (E) at amino acid position 146 to be replaced by an aspartic acid (D). 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

0.12

BayesDel_addAF

Benign

0.0036

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.57

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.047

MetaRNN

Benign

0.37

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.33

PrimateAI

Uncertain

0.56

Sift4G

Benign

0.40

Polyphen

0.54

Vest4

0.55

MutPred

0.28

Loss of stability (P = 0.0824);

MVP

0.78

MPC

0.85

ClinPred

0.33

GERP RS

2.9

Varity_R

0.072

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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