Genetic Variant RAB29:p.Gln104Glu (chr1-205771540-G-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_003929.3(RAB29):c.310C>G(p.Gln104Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0146 in 1,614,136 control chromosomes in the GnomAD database, including 256 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0098 ( 13 hom., cov: 32)

Exomes 𝑓: 0.015 ( 243 hom. )

Consequence

RAB29
NM_003929.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.02

Publications

9 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007671267).

BP6

Variant 1-205771540-G-C is Benign according to our data. Variant chr1-205771540-G-C is described in ClinVar as Benign. ClinVar VariationId is 3037484.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00979 (1491/152288) while in subpopulation SAS AF = 0.0249 (120/4822). AF 95% confidence interval is 0.0213. There are 13 homozygotes in GnomAd4. There are 748 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB29	NM_003929.3 link	c.310C>G	p.Gln104Glu	missense_variant	Exon 4 of 6	ENST00000367139.8	NP_003920.1	O14966-1Q6FGU7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB29	ENST00000367139.8 link	c.310C>G	p.Gln104Glu	missense_variant	Exon 4 of 6	1	NM_003929.3	ENSP00000356107.3		O14966-1

Frequencies

GnomAD3 genomes

AF:

0.00982

AC:

1494

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00232

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.00635

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0249

Gnomad FIN

AF:

0.0124

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0143

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.0125

AC:

3142

AN:

251490

AF XY:

0.0140

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.00416

Gnomad ASJ exome

AF:

0.0121

Gnomad EAS exome

AF:

0.000217

Gnomad FIN exome

AF:

0.0134

Gnomad NFE exome

AF:

0.0139

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.0151

AC:

22117

AN:

1461848

Hom.:

243

Cov.:

AF XY:

0.0157

AC XY:

11429

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00218

AC:

AN:

33480

American (AMR)

AF:

0.00454

AC:

203

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0108

AC:

283

AN:

26136

East Asian (EAS)

AF:

0.000151

AC:

AN:

39700

South Asian (SAS)

AF:

0.0303

AC:

2617

AN:

86252

European-Finnish (FIN)

AF:

0.0125

AC:

667

AN:

53420

Middle Eastern (MID)

AF:

0.0212

AC:

122

AN:

5766

European-Non Finnish (NFE)

AF:

0.0155

AC:

17254

AN:

1111974

Other (OTH)

AF:

0.0148

AC:

892

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

1331

2661

3992

5322

6653

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

688

1376

2064

2752

3440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00979

AC:

1491

AN:

152288

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

748

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00231

AC:

AN:

41564

American (AMR)

AF:

0.00627

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0115

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.0249

AC:

120

AN:

4822

European-Finnish (FIN)

AF:

0.0124

AC:

132

AN:

10612

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0143

AC:

970

AN:

68022

Other (OTH)

AF:

0.0104

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

154

230

307

384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0126

Hom.:

Bravo

AF:

0.00868

TwinsUK

AF:

0.0138

AC:

ALSPAC

AF:

0.0179

AC:

ESP6500AA

AF:

0.00386

AC:

ESP6500EA

AF:

0.0143

AC:

123

ExAC

AF:

0.0128

AC:

1559

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0157

EpiControl

AF:

0.0152

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RAB29-related disorder

Benign:1

Jun 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.45

DEOGEN2

Benign

0.15

T;T;.;.;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.049

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

.;.;D;D;D

MetaRNN

Benign

0.0077

T;T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

-0.45

N;N;.;.;N

PhyloP100

5.0

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.15

N;N;N;N;N

REVEL

Benign

0.26

Sift

Benign

0.95

T;T;T;T;T

Sift4G

Benign

0.96

T;T;T;T;T

Polyphen

0.0010

B;B;.;.;B

Vest4

0.098

MPC

0.50

ClinPred

0.038

GERP RS

5.3

Varity_R

0.22

gMVP

0.46

Mutation Taster

=77/23

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over