Variant chr1-156070189-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020387.4(RAB25):c.544C>G(p.Gln182Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,614,092 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00083 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0010 ( 0 hom. )

Consequence

RAB25
NM_020387.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.48

Variant links:

Genes affected

RAB25 (HGNC:18238): (RAB25, member RAS oncogene family) The protein encoded by this gene is a member of the RAS superfamily of small GTPases. The encoded protein is involved in membrane trafficking and cell survival. This gene has been found to be a tumor suppressor and an oncogene, depending on the context. Two variants, one protein-coding and the other not, have been found for this gene. [provided by RefSeq, Nov 2015]

RAB25 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.015416086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB25	NM_020387.4 linkuse as main transcript	c.544C>G	p.Gln182Glu	missense_variant	5/5	ENST00000361084.10
RAB25	NR_133653.2 linkuse as main transcript	n.589C>G		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
RAB25	ENST00000361084.10 linkuse as main transcript	c.544C>G	p.Gln182Glu	missense_variant	5/5	1	NM_020387.4	P1
RAB25	ENST00000497968.1 linkuse as main transcript	n.363C>G		non_coding_transcript_exon_variant	3/3	1
RAB25	ENST00000473336.5 linkuse as main transcript	n.366C>G		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes

AF:

0.000835

AC:

127

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

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:

0.00137

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000620

AC:

154

AN:

248556

Hom.:

AF XY:

0.000600

AC XY:

AN XY:

134954

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.000753

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:

0.00108

Gnomad OTH exome

AF:

0.000660

GnomAD4 exome

AF:

0.00102

AC:

1490

AN:

1461878

Hom.:

Cov.:

AF XY:

0.000982

AC XY:

714

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00126

Gnomad4 OTH exome

AF:

0.000729

GnomAD4 genome

AF:

0.000834

AC:

127

AN:

152214

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00137

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000871

Hom.:

Bravo

AF:

0.000975

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000246

AC:

ESP6500EA

AF:

0.00191

AC:

ExAC

AF:

0.000678

AC:

EpiCase

AF:

0.000872

EpiControl

AF:

0.00119

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

Jan 04, 2024

The c.544C>G (p.Q182E) alteration is located in exon 5 (coding exon 5) of the RAB25 gene. This alteration results from a C to G substitution at nucleotide position 544, causing the glutamine (Q) at amino acid position 182 to be replaced by a glutamic acid (E). 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

0.078

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.58

DEOGEN2

Benign

0.042

Eigen

Benign

-0.11

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.83

M_CAP

Benign

0.0076

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.95

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.33

REVEL

Uncertain

0.31

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.020

Vest4

0.13

MVP

0.83

MPC

0.27

ClinPred

0.020

GERP RS

6.0

Varity_R

0.15

gMVP

0.42

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