Variant chr1-156066019-C-T 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_020387.4(RAB25):c.152C>T(p.Thr51Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,754 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: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

RAB25
NM_020387.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.80

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:

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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, 0.925

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB25	NM_020387.4 linkuse as main transcript	c.152C>T	p.Thr51Ile	missense_variant	2/5	ENST00000361084.10
RAB25	NR_133653.2 linkuse as main transcript	n.285-2251C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
RAB25	ENST00000361084.10 linkuse as main transcript	c.152C>T	p.Thr51Ile	missense_variant	2/5	1	NM_020387.4	P1
RAB25	ENST00000463614.1 linkuse as main transcript	n.364C>T		non_coding_transcript_exon_variant	2/2	2
RAB25	ENST00000473336.5 linkuse as main transcript	n.62-2251C>T		intron_variant, non_coding_transcript_variant		2
RAB25	ENST00000487325.5 linkuse as main transcript	n.239-2251C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461754

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727178

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.00000825

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

Nov 07, 2022

The c.152C>T (p.T51I) alteration is located in exon 2 (coding exon 2) of the RAB25 gene. This alteration results from a C to T substitution at nucleotide position 152, causing the threonine (T) at amino acid position 51 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

Pathogenic

0.90

BayesDel_addAF

Pathogenic

0.39

BayesDel_noAF

Pathogenic

0.32

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.65

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.081

MetaRNN

Pathogenic

0.92

MetaSVM

Uncertain

0.13

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-5.7

REVEL

Pathogenic

0.81

Sift

Pathogenic

0.0

Sift4G

Benign

0.066

Polyphen

1.0

Vest4

0.95

MVP

0.92

MPC

0.92

ClinPred

1.0

GERP RS

5.3

Varity_R

0.92

gMVP

0.74

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