Variant 16-2152860-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014353.5(RAB26):c.509T>C(p.Val170Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,418 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RAB26
NM_014353.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.94

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]

RAB26 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB26	NM_014353.5 link	c.509T>C	p.Val170Ala	missense_variant	6/9	ENST00000210187.11	NP_055168.2	Q9ULW5-1
RAB26	NM_001308053.1 link	c.311T>C	p.Val104Ala	missense_variant	7/10		NP_001294982.1	Q9ULW5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB26	ENST00000210187.11 link	c.509T>C	p.Val170Ala	missense_variant	6/9	1	NM_014353.5	ENSP00000210187.6		Q9ULW5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000816

AC:

AN:

245140

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133478

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000297

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:

0.00000904

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1455418

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

723524

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000228

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:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000825

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Apr 20, 2024

The c.509T>C (p.V170A) alteration is located in exon 6 (coding exon 6) of the RAB26 gene. This alteration results from a T to C substitution at nucleotide position 509, causing the valine (V) at amino acid position 170 to be replaced by an alanine (A). 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

0.23

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.54

.;D

Eigen

Benign

0.18

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

T;T

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.72

D;D

MetaSVM

Uncertain

-0.28

MutationAssessor

Benign

1.1

.;L

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.8

D;D

REVEL

Pathogenic

0.76

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.030

D;D

Polyphen

0.97

.;D

Vest4

0.45

MutPred

0.80

.;Loss of sheet (P = 0.0817);

MVP

0.61

MPC

0.17

ClinPred

0.61

GERP RS

2.9

Varity_R

0.51

gMVP

0.79

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over