Variant chr16-2149998-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014353.5(RAB26):c.253G>A(p.Asp85Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000762 in 1,545,370 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00081 ( 4 hom. )

Consequence

RAB26
NM_014353.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.39

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16252947).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB26	NM_014353.5 link	c.253G>A	p.Asp85Asn	missense_variant	2/9	ENST00000210187.11	NP_055168.2	Q9ULW5-1
RAB26	NM_001308053.1 link	c.55G>A	p.Asp19Asn	missense_variant	3/10		NP_001294982.1	Q9ULW5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB26	ENST00000210187.11 link	c.253G>A	p.Asp85Asn	missense_variant	2/9	1	NM_014353.5	ENSP00000210187.6		Q9ULW5-1

Frequencies

GnomAD3 genomes

AF:

0.000342

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000706

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000356

AC:

AN:

151770

Hom.:

AF XY:

0.000350

AC XY:

AN XY:

79952

show subpopulations

Gnomad AFR exome

AF:

0.000118

Gnomad AMR exome

AF:

0.00

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:

0.000879

Gnomad OTH exome

AF:

0.000236

GnomAD4 exome

AF:

0.000808

AC:

1125

AN:

1393142

Hom.:

Cov.:

AF XY:

0.000732

AC XY:

503

AN XY:

686970

show subpopulations

Gnomad4 AFR exome

AF:

0.0000960

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:

0.000957

Gnomad4 OTH exome

AF:

0.00159

GnomAD4 genome

AF:

0.000342

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000706

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000496

Hom.:

Bravo

AF:

0.000431

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000488

AC:

ExAC

AF:

0.000123

AC:

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

Oct 08, 2024

The c.253G>A (p.D85N) alteration is located in exon 2 (coding exon 2) of the RAB26 gene. This alteration results from a G to A substitution at nucleotide position 253, causing the aspartic acid (D) at amino acid position 85 to be replaced by an asparagine (N). 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

Pathogenic

0.63

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.54

.;D

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.96

D;D

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.16

T;T

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

0.29

.;N

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.9

D;D

REVEL

Uncertain

0.41

Sift

Uncertain

0.016

D;D

Sift4G

Uncertain

0.025

D;D

Polyphen

0.81

.;P

Vest4

0.31

MVP

0.79

MPC

0.56

ClinPred

0.39

GERP RS

4.2

Varity_R

0.39

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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