16-2148826-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014353.5(RAB26):​c.43C>T​(p.Pro15Ser) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RAB26
NM_014353.5 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.417
Variant links:
Genes affected
RAB26 (HGNC:14259): (RAB26, member RAS oncogene family) Members of the RAB protein family, including RAB26, are important regulators of vesicular fusion and trafficking. The RAB family of small G proteins regulates intercellular vesicle trafficking, including exocytosis, endocytosis, and recycling (summary by Seki et al., 2000 [PubMed 11043516]).[supplied by OMIM, Nov 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23624504).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAB26NM_014353.5 linkc.43C>T p.Pro15Ser missense_variant Exon 1 of 9 ENST00000210187.11 NP_055168.2 Q9ULW5-1
RAB26NM_001308053.1 linkc.-156C>T 5_prime_UTR_variant Exon 2 of 10 NP_001294982.1 Q9ULW5-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAB26ENST00000210187.11 linkc.43C>T p.Pro15Ser missense_variant Exon 1 of 9 1 NM_014353.5 ENSP00000210187.6 Q9ULW5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1263632
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
622104
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 06, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.43C>T (p.P15S) alteration is located in exon 1 (coding exon 1) of the RAB26 gene. This alteration results from a C to T substitution at nucleotide position 43, causing the proline (P) at amino acid position 15 to be replaced by a serine (S). 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
Benign
0.069
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
10
DANN
Benign
0.88
DEOGEN2
Benign
0.019
T
Eigen
Benign
-0.80
Eigen_PC
Benign
-0.79
FATHMM_MKL
Benign
0.045
N
LIST_S2
Benign
0.69
T
M_CAP
Pathogenic
0.81
D
MetaRNN
Benign
0.24
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.0
L
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-0.51
N
REVEL
Benign
0.038
Sift
Benign
0.097
T
Sift4G
Benign
0.20
T
Polyphen
0.018
B
Vest4
0.23
MutPred
0.20
Gain of phosphorylation at P15 (P = 0.0218);
MVP
0.56
MPC
0.12
ClinPred
0.056
T
GERP RS
2.7
Varity_R
0.061
gMVP
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: chr16-2198827; API