Variant chr1-205770427-T-A 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_003929.3(RAB29):c.527A>T(p.Asn176Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,192 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 (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

RAB29
NM_003929.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.48

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23018375).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB29	NM_003929.3 linkuse as main transcript	c.527A>T	p.Asn176Ile	missense_variant	6/6	ENST00000367139.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB29	ENST00000367139.8 linkuse as main transcript	c.527A>T	p.Asn176Ile	missense_variant	6/6	1	NM_003929.3	P1	O14966-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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

Mar 17, 2023

The c.527A>T (p.N176I) alteration is located in exon 6 (coding exon 5) of the RAB29 gene. This alteration results from a A to T substitution at nucleotide position 527, causing the asparagine (N) at amino acid position 176 to be replaced by an isoleucine (I). 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

Uncertain

0.045

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

T;T;.;.;T

Eigen

Benign

0.012

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.87

.;.;D;D;D

M_CAP

Benign

0.031

MetaRNN

Benign

0.23

T;T;T;T;T

MetaSVM

Uncertain

-0.24

MutationAssessor

Uncertain

2.1

M;M;.;.;M

MutationTaster

Benign

0.66

D;D;D;D;D

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.5

D;D;D;D;D

REVEL

Uncertain

0.31

Sift

Benign

0.059

T;T;T;T;T

Sift4G

Benign

0.15

T;T;T;T;T

Polyphen

0.054

B;B;.;.;B

Vest4

0.29

MutPred

0.35

Loss of disorder (P = 0.0273);Loss of disorder (P = 0.0273);.;.;Loss of disorder (P = 0.0273);

MVP

0.63

MPC

0.55

ClinPred

0.89

GERP RS

5.4

Varity_R

0.44

gMVP

0.67

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

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