chr14-64971977-G-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001308154.2(RAB15):c.100C>T(p.His34Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
RAB15
NM_001308154.2 missense
NM_001308154.2 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 2.55
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 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3719499).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RAB15 | NM_001308154.2 | c.100C>T | p.His34Tyr | missense_variant | 1/7 | ENST00000533601.7 | NP_001295083.1 | |
CHURC1-FNTB | NM_001202559.1 | c.328-32272G>A | intron_variant | NP_001189488.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RAB15 | ENST00000533601.7 | c.100C>T | p.His34Tyr | missense_variant | 1/7 | 1 | NM_001308154.2 | ENSP00000434103 | P1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD3 exomes AF: 0.00000456 AC: 1AN: 219064Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 118436
GnomAD3 exomes
AF:
AC:
1
AN:
219064
Hom.:
AF XY:
AC XY:
0
AN XY:
118436
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000139 AC: 2AN: 1443250Hom.: 0 Cov.: 32 AF XY: 0.00000279 AC XY: 2AN XY: 716308
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
2
AN:
1443250
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
716308
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 31
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 submitter | clinical testing | Ambry Genetics | Jan 23, 2024 | The c.100C>T (p.H34Y) alteration is located in exon 1 (coding exon 1) of the RAB15 gene. This alteration results from a C to T substitution at nucleotide position 100, causing the histidine (H) at amino acid position 34 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
.;D;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.;.
MutationTaster
Benign
D;D;N;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;.;.
REVEL
Benign
Sift
Benign
T;D;.;.
Sift4G
Uncertain
T;D;.;.
Polyphen
P;.;.;.
Vest4
MutPred
Loss of disorder (P = 0.0245);Loss of disorder (P = 0.0245);.;.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at