Variant 1-205770812-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003929.3(RAB29):c.421C>G(p.Arg141Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000669 in 1,613,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R141Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

RAB29
NM_003929.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.90

Variant links:

Genes affected

RAB29 (HGNC:9789): (RAB29, member RAS oncogene family) Enables several functions, including dynein complex binding activity; guanyl ribonucleotide binding activity; and kinesin binding activity. Involved in several processes, including positive regulation of T cell receptor signaling pathway; positive regulation of receptor recycling; and toxin transport. Located in several cellular components, including Golgi apparatus; endosome; and vacuole. [provided by Alliance of Genome Resources, Apr 2022]

RAB29 links:

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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=0.3406972).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB29	NM_003929.3 linkuse as main transcript	c.421C>G	p.Arg141Gly	missense_variant	5/6	ENST00000367139.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB29	ENST00000367139.8 linkuse as main transcript	c.421C>G	p.Arg141Gly	missense_variant	5/6	1	NM_003929.3	P1	O14966-1

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152082

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:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251424

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135886

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:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000650

AC:

AN:

1461826

Hom.:

Cov.:

AF XY:

0.0000481

AC XY:

AN XY:

727210

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:

0.0000827

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000855

AC:

AN:

152082

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74276

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:

0.000191

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000869

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

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

Aug 16, 2021

The c.421C>G (p.R141G) alteration is located in exon 5 (coding exon 4) of the RAB29 gene. This alteration results from a C to G substitution at nucleotide position 421, causing the arginine (R) at amino acid position 141 to be replaced by a glycine (G). 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

0.13

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.0

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.51

D;D;.;.;D

Eigen

Benign

-0.016

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.94

M_CAP

Benign

0.034

MetaRNN

Benign

0.34

T;T;T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Benign

1.1

L;L;.;.;L

MutationTaster

Benign

0.91

D;D;D;D;D

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.7

D;D;N;D;D

REVEL

Uncertain

0.38

Sift

Uncertain

0.020

D;D;D;D;D

Sift4G

Benign

0.083

T;T;T;T;T

Polyphen

0.0

B;B;.;.;B

Vest4

0.48

MVP

0.80

MPC

0.66

ClinPred

0.82

GERP RS

5.3

Varity_R

0.39

gMVP

0.62

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