chr14-64972058-C-T

Variant summary

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

The NM_001308154.2(RAB15):​c.19G>A​(p.Val7Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,798 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RAB15
NM_001308154.2 missense

Scores

3
5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.49
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]

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/exons MANE Protein UniProt
RAB15NM_001308154.2 linkuse as main transcriptc.19G>A p.Val7Met missense_variant 1/7 ENST00000533601.7 NP_001295083.1
CHURC1-FNTBNM_001202559.1 linkuse as main transcriptc.328-32191C>T intron_variant NP_001189488.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RAB15ENST00000533601.7 linkuse as main transcriptc.19G>A p.Val7Met missense_variant 1/71 NM_001308154.2 ENSP00000434103 P1P59190-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1457798
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
725128
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

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 submitterclinical testingAmbry GeneticsFeb 16, 2023The c.19G>A (p.V7M) alteration is located in exon 1 (coding exon 1) of the RAB15 gene. This alteration results from a G to A substitution at nucleotide position 19, causing the valine (V) at amino acid position 7 to be replaced by a methionine (M). 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
0.63
BayesDel_addAF
Benign
-0.0036
T
BayesDel_noAF
Benign
-0.24
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.015
.;T;.;.
Eigen
Benign
0.058
Eigen_PC
Benign
0.090
FATHMM_MKL
Benign
0.69
D
LIST_S2
Uncertain
0.95
D;D;D;D
M_CAP
Pathogenic
0.90
D
MetaRNN
Uncertain
0.48
T;T;T;T
MetaSVM
Uncertain
-0.27
T
MutationAssessor
Benign
-0.26
N;N;.;.
MutationTaster
Benign
1.0
D;D;N;N
PrimateAI
Pathogenic
0.92
D
PROVEAN
Benign
0.21
N;N;.;.
REVEL
Uncertain
0.45
Sift
Benign
0.095
T;T;.;.
Sift4G
Benign
0.079
T;T;.;.
Polyphen
0.90
P;.;.;.
Vest4
0.34
MutPred
0.53
Gain of disorder (P = 0.0713);Gain of disorder (P = 0.0713);.;.;
MVP
0.85
MPC
0.82
ClinPred
0.52
D
GERP RS
3.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.22
gMVP
0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-65438776; API