rs367753617

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001308154.2(RAB15):​c.280C>T​(p.Arg94Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,612,404 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R94S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

RAB15
NM_001308154.2 missense

Scores

7
9
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.94
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]
CHURC1-FNTB (HGNC:42960): (CHURC1-FNTB readthrough) This locus represents naturally occurring read-through transcription between the neighboring CHURC1 (churchill domain containing 1) and FNTB (farnesyltransferase, CAAX box, beta) on chromosome 14. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Feb 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAB15NM_001308154.2 linkc.280C>T p.Arg94Cys missense_variant Exon 4 of 7 ENST00000533601.7 NP_001295083.1 P59190-1G5EMR8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAB15ENST00000533601.7 linkc.280C>T p.Arg94Cys missense_variant Exon 4 of 7 1 NM_001308154.2 ENSP00000434103.3 P59190-1
CHURC1-FNTBENST00000549987.1 linkc.246+25038G>A intron_variant Intron 3 of 13 2 ENSP00000447121.2 B4DL54

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152124
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000266
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:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000360
AC:
9
AN:
249786
Hom.:
0
AF XY:
0.0000444
AC XY:
6
AN XY:
135164
show subpopulations
Gnomad AFR exome
AF:
0.000247
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.0000492
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000240
AC:
35
AN:
1460280
Hom.:
0
Cov.:
32
AF XY:
0.0000262
AC XY:
19
AN XY:
726552
show subpopulations
Gnomad4 AFR exome
AF:
0.000329
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000153
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152124
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.000266
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:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000250
Hom.:
0
Bravo
AF:
0.000136
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Uncertain
0.059
T
BayesDel_noAF
Pathogenic
0.14
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.53
.;D;D;.;.;.
Eigen
Pathogenic
0.80
Eigen_PC
Pathogenic
0.82
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
D;D;T;D;D;D
M_CAP
Uncertain
0.22
D
MetaRNN
Uncertain
0.69
D;D;D;D;D;D
MetaSVM
Uncertain
0.22
D
MutationAssessor
Benign
1.4
L;L;.;.;.;.
PrimateAI
Pathogenic
0.84
D
PROVEAN
Pathogenic
-4.9
D;D;D;.;.;.
REVEL
Uncertain
0.61
Sift
Uncertain
0.0020
D;D;D;.;.;.
Sift4G
Uncertain
0.011
D;D;.;.;.;.
Polyphen
1.0
D;.;.;.;.;.
Vest4
0.59
MVP
0.93
MPC
1.6
ClinPred
0.58
D
GERP RS
5.6
Varity_R
0.44
gMVP
0.60

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.

Other links and lift over

dbSNP: rs367753617; hg19: chr14-65417836; COSMIC: COSV99962232; COSMIC: COSV99962232; API