chr14-64951082-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001308154.2(RAB15):​c.316G>A​(p.Val106Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000349 in 1,460,814 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: 0.000035 ( 0 hom. )

Consequence

RAB15
NM_001308154.2 missense

Scores

9
7
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.06
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.825

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RAB15NM_001308154.2 linkuse as main transcriptc.316G>A p.Val106Met missense_variant 4/7 ENST00000533601.7 NP_001295083.1
CHURC1-FNTBNM_001202559.1 linkuse as main transcriptc.327+25002C>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.316G>A p.Val106Met missense_variant 4/71 NM_001308154.2 ENSP00000434103 P1P59190-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000439
AC:
11
AN:
250356
Hom.:
0
AF XY:
0.0000517
AC XY:
7
AN XY:
135398
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000968
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000349
AC:
51
AN:
1460814
Hom.:
0
Cov.:
31
AF XY:
0.0000385
AC XY:
28
AN XY:
726772
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000191
Gnomad4 NFE exome
AF:
0.0000405
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000471
Hom.:
0
ExAC
AF:
0.0000659
AC:
8

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 GeneticsJan 24, 2024The c.316G>A (p.V106M) alteration is located in exon 4 (coding exon 4) of the RAB15 gene. This alteration results from a G to A substitution at nucleotide position 316, causing the valine (V) at amino acid position 106 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
0.81
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
0.12
CADD
Pathogenic
32
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.44
.;T;T;.;.;.
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.96
D;D;D;D;D;D
M_CAP
Pathogenic
0.37
D
MetaRNN
Pathogenic
0.83
D;D;D;D;D;D
MetaSVM
Uncertain
0.32
D
MutationAssessor
Benign
1.8
L;L;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-2.2
N;N;N;.;.;.
REVEL
Pathogenic
0.65
Sift
Pathogenic
0.0
D;D;D;.;.;.
Sift4G
Pathogenic
0.0010
D;D;.;.;.;.
Polyphen
1.0
D;.;.;.;.;.
Vest4
0.63
MutPred
0.74
Gain of ubiquitination at K101 (P = 0.0754);Gain of ubiquitination at K101 (P = 0.0754);.;.;.;.;
MVP
0.91
MPC
1.6
ClinPred
0.43
T
GERP RS
5.6
Varity_R
0.58
gMVP
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs758496557; hg19: chr14-65417800; API