16-2148865-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014353.5(RAB26):​c.82C>T​(p.Pro28Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,402,952 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00051 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00010 ( 1 hom. )

Consequence

RAB26
NM_014353.5 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.963
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.008869141).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAB26NM_014353.5 linkc.82C>T p.Pro28Ser missense_variant Exon 1 of 9 ENST00000210187.11 NP_055168.2 Q9ULW5-1
RAB26NM_001308053.1 linkc.-117C>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.82C>T p.Pro28Ser missense_variant Exon 1 of 9 1 NM_014353.5 ENSP00000210187.6 Q9ULW5-1

Frequencies

GnomAD3 genomes
AF:
0.000506
AC:
77
AN:
152032
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00118
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00105
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.000327
AC:
20
AN:
61178
Hom.:
0
AF XY:
0.000247
AC XY:
9
AN XY:
36430
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000456
Gnomad ASJ exome
AF:
0.00270
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000413
Gnomad OTH exome
AF:
0.00123
GnomAD4 exome
AF:
0.000103
AC:
129
AN:
1250812
Hom.:
1
Cov.:
31
AF XY:
0.000107
AC XY:
66
AN XY:
614084
show subpopulations
Gnomad4 AFR exome
AF:
0.00190
Gnomad4 AMR exome
AF:
0.000317
Gnomad4 ASJ exome
AF:
0.00146
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000159
Gnomad4 OTH exome
AF:
0.000335
GnomAD4 genome
AF:
0.000513
AC:
78
AN:
152140
Hom.:
0
Cov.:
32
AF XY:
0.000484
AC XY:
36
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.00120
Gnomad4 AMR
AF:
0.00105
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.000427
Hom.:
0
Bravo
AF:
0.000536
ExAC
AF:
0.0000793
AC:
8
Asia WGS
AF:
0.000291
AC:
1
AN:
3454

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 16, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.82C>T (p.P28S) 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 82, causing the proline (P) at amino acid position 28 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
0.074
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
8.3
DANN
Benign
0.69
DEOGEN2
Benign
0.016
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.044
N
LIST_S2
Benign
0.59
T
M_CAP
Pathogenic
0.49
D
MetaRNN
Benign
0.0089
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-0.26
N
REVEL
Benign
0.026
Sift
Benign
0.16
T
Sift4G
Benign
0.27
T
Polyphen
0.0
B
Vest4
0.077
MutPred
0.22
Gain of phosphorylation at P28 (P = 0.0087);
MVP
0.22
MPC
0.17
ClinPred
0.016
T
GERP RS
2.0
Varity_R
0.035
gMVP
0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs771023224; hg19: chr16-2198866; API