16-2153359-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.709C>T​(p.Arg237Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.0000062 ( 0 hom. )

Consequence

RAB26
NM_014353.5 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.67
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=0.24514493).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAB26NM_014353.5 linkc.709C>T p.Arg237Cys missense_variant Exon 9 of 9 ENST00000210187.11 NP_055168.2 Q9ULW5-1
RAB26NM_001308053.1 linkc.511C>T p.Arg171Cys missense_variant Exon 10 of 10 NP_001294982.1 Q9ULW5-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAB26ENST00000210187.11 linkc.709C>T p.Arg237Cys missense_variant Exon 9 of 9 1 NM_014353.5 ENSP00000210187.6 Q9ULW5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250566
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135742
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:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000885
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461198
Hom.:
0
Cov.:
34
AF XY:
0.00000550
AC XY:
4
AN XY:
726892
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 25, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.709C>T (p.R237C) alteration is located in exon 9 (coding exon 9) of the RAB26 gene. This alteration results from a C to T substitution at nucleotide position 709, causing the arginine (R) at amino acid position 237 to be replaced by a cysteine (C). 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
0.087
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.35
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
.;T
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.38
FATHMM_MKL
Benign
0.70
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Uncertain
0.14
D
MetaRNN
Benign
0.25
T;T
MetaSVM
Benign
-0.74
T
MutationAssessor
Benign
1.7
.;L
PrimateAI
Benign
0.22
T
PROVEAN
Uncertain
-3.7
D;D
REVEL
Benign
0.12
Sift
Uncertain
0.022
D;D
Sift4G
Uncertain
0.026
D;D
Polyphen
0.99
.;D
Vest4
0.34
MutPred
0.35
.;Loss of MoRF binding (P = 0.0126);
MVP
0.66
MPC
0.43
ClinPred
1.0
D
GERP RS
2.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.11
gMVP
0.44

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs780018086; hg19: chr16-2203360; COSMIC: COSV52954309; COSMIC: COSV52954309; API