Variant 1-205772499-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_003929.3(RAB29):c.193G>T(p.Ala65Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RAB29
NM_003929.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.92

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:

RAB29 (HGNC:):

RAB29 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.938

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB29	NM_003929.3 linkuse as main transcript	c.193G>T	p.Ala65Ser	missense_variant	3/6	ENST00000367139.8	NP_003920.1	O14966-1Q6FGU7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB29	ENST00000367139.8 linkuse as main transcript	c.193G>T	p.Ala65Ser	missense_variant	3/6	1	NM_003929.3	ENSP00000356107.3		O14966-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251448

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135908

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:

0.00000879

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461578

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727128

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 17, 2023

The c.193G>T (p.A65S) alteration is located in exon 3 (coding exon 2) of the RAB29 gene. This alteration results from a G to T substitution at nucleotide position 193, causing the alanine (A) at amino acid position 65 to be replaced by a serine (S). 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

Pathogenic

0.66

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;D;D

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.97

.;.;D

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.94

D;D;D

MetaSVM

Pathogenic

0.87

MutationAssessor

Uncertain

2.1

M;M;M

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-2.8

D;D;D

REVEL

Pathogenic

0.86

Sift

Uncertain

0.0020

D;D;D

Sift4G

Benign

0.090

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.86

MutPred

0.86

Loss of catalytic residue at A65 (P = 0.0141);Loss of catalytic residue at A65 (P = 0.0141);Loss of catalytic residue at A65 (P = 0.0141);

MVP

0.86

MPC

1.2

ClinPred

0.95

GERP RS

5.3

Varity_R

0.79

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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