Genetic Variant RAB26:p.Thr6Ile (chr16-2148800-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014353.5(RAB26):c.17C>T(p.Thr6Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000795 in 1,383,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000032 ( 0 hom. )

Consequence

RAB26
NM_014353.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25789788).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014353.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB26	NM_014353.5	MANE Select	c.17C>T	p.Thr6Ile	missense	Exon 1 of 9	NP_055168.2
	RAB26	NM_001308053.1		c.-182C>T		5_prime_UTR	Exon 2 of 10	NP_001294982.1	Q9ULW5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAB26	ENST00000210187.11	TSL:1 MANE Select	c.17C>T	p.Thr6Ile	missense	Exon 1 of 9	ENSP00000210187.6	Q9ULW5-1
RAB26	ENST00000541451.5	TSL:1	c.-182C>T		5_prime_UTR	Exon 2 of 10	ENSP00000441580.1	Q9ULW5-2
RAB26	ENST00000564426.5	TSL:1	n.61C>T		non_coding_transcript_exon	Exon 2 of 9

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

151804

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.000479

GnomAD4 exome

AF:

0.00000325

AC:

AN:

1232078

Hom.:

Cov.:

AF XY:

0.00000165

AC XY:

AN XY:

604654

show subpopulations

African (AFR)

AF:

0.0000408

AC:

AN:

24536

American (AMR)

AF:

0.00

AC:

AN:

14982

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18052

East Asian (EAS)

AF:

0.00

AC:

AN:

28266

South Asian (SAS)

AF:

0.0000191

AC:

AN:

52486

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34522

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4558

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1004752

Other (OTH)

AF:

0.0000401

AC:

AN:

49924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000461

AC:

AN:

151804

Hom.:

Cov.:

AF XY:

0.0000809

AC XY:

AN XY:

74138

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41384

American (AMR)

AF:

0.0000655

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10470

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67902

Other (OTH)

AF:

0.000479

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000453

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.036

Eigen

Benign

-0.080

Eigen_PC

Benign

-0.10

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.85

M_CAP

Pathogenic

0.97

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.1

PhyloP100

1.3

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.0

REVEL

Benign

0.097

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.014

Polyphen

0.84

Vest4

0.14

MutPred

0.23

Loss of phosphorylation at T6 (P = 0.0016)

MVP

0.68

MPC

0.21

ClinPred

0.84

GERP RS

4.1

PromoterAI

0.16

Neutral

(source)

Varity_R

0.18

gMVP

0.41

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over