Variant chr14-64971998-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP3BP4_Strong

The NM_001308154.2(RAB15):c.79C>G(p.Arg27Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,606,236 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 0.00015 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

RAB15
NM_001308154.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.15

Variant links:

Genes affected

RAB15 (HGNC:20150): (RAB15, member RAS oncogene family) Predicted to enable GTP binding activity and GTPase activity. Involved in positive regulation of regulated secretory pathway. Located in cilium; endosome membrane; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RAB15 links:

CHURC1-FNTB (HGNC:):

CHURC1-FNTB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Multiple lines of computational evidence support a deleterious effect 9: AlphaMissense, BayesDel_addAF, BayesDel_noAF, Cadd, M_CAP, MutationAssessor, PrimateAI, PROVEAN, REVEL [when max_spliceai, Eigen, FATHMM_MKL, MetaRNN, MutationTaster, phyloP100way_vertebrate was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.035076916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB15	NM_001308154.2 linkuse as main transcript	c.79C>G	p.Arg27Gly	missense_variant	1/7	ENST00000533601.7	NP_001295083.1
CHURC1-FNTB	NM_001202559.1 linkuse as main transcript	c.328-32251G>C		intron_variant			NP_001189488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB15	ENST00000533601.7 linkuse as main transcript	c.79C>G	p.Arg27Gly	missense_variant	1/7	1	NM_001308154.2	ENSP00000434103	P1	P59190-1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000268

AC:

AN:

235166

Hom.:

AF XY:

0.000258

AC XY:

AN XY:

127662

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00606

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000492

Gnomad NFE exome

AF:

0.0000287

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000140

AC:

204

AN:

1454174

Hom.:

Cov.:

AF XY:

0.000141

AC XY:

102

AN XY:

722722

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00598

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.0000280

Gnomad4 OTH exome

AF:

0.000266

GnomAD4 genome

AF:

0.000151

AC:

AN:

152062

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000541

Hom.:

Bravo

AF:

0.000200

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000182

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

Aug 12, 2021

The c.79C>G (p.R27G) alteration is located in exon 1 (coding exon 1) of the RAB15 gene. This alteration results from a C to G substitution at nucleotide position 79, causing the arginine (R) at amino acid position 27 to be replaced by a glycine (G). 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

0.98

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.30

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.67

.;D;.;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.87

D;D;D;D

M_CAP

Pathogenic

0.92

MetaRNN

Benign

0.035

T;T;T;T

MetaSVM

Benign

-0.42

MutationAssessor

Pathogenic

4.5

H;H;.;.

MutationTaster

Benign

1.0

D;D;N;N

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-6.3

D;D;.;.

REVEL

Pathogenic

0.69

Sift

Pathogenic

0.0

D;D;.;.

Sift4G

Pathogenic

0.0

D;D;.;.

Polyphen

0.082

B;.;.;.

Vest4

0.71

MVP

0.91

MPC

1.9

ClinPred

0.55

GERP RS

1.4

Varity_R

0.92

gMVP

0.85

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