Genetic Variant RAB26:p.Pro28Ser (chr16-2148865-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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. 15/22 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

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.963

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008869141).

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.82C>T	p.Pro28Ser	missense	Exon 1 of 9	NP_055168.2
	RAB26	NM_001308053.1		c.-117C>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.82C>T	p.Pro28Ser	missense	Exon 1 of 9	ENSP00000210187.6	Q9ULW5-1
RAB26	ENST00000541451.5	TSL:1	c.-117C>T		5_prime_UTR	Exon 2 of 10	ENSP00000441580.1	Q9ULW5-2
RAB26	ENST00000564426.5	TSL:1	n.126C>T		non_coding_transcript_exon	Exon 2 of 9

Frequencies

GnomAD3 genomes

AF:

0.000506

AC:

AN:

152032

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000327

AC:

AN:

61178

AF XY:

0.000247

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 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.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

614084

show subpopulations

African (AFR)

AF:

0.00190

AC:

AN:

25300

American (AMR)

AF:

0.000317

AC:

AN:

18954

Ashkenazi Jewish (ASJ)

AF:

0.00146

AC:

AN:

20604

East Asian (EAS)

AF:

0.00

AC:

AN:

27696

South Asian (SAS)

AF:

0.00

AC:

AN:

59238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35014

Middle Eastern (MID)

AF:

0.00262

AC:

AN:

4572

European-Non Finnish (NFE)

AF:

0.0000159

AC:

AN:

1008634

Other (OTH)

AF:

0.000335

AC:

AN:

50800

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.000513

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.00120

AC:

AN:

41546

American (AMR)

AF:

0.00105

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67960

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.000427

Hom.:

Bravo

AF:

0.000536

ExAC

AF:

0.0000793

AC:

Asia WGS

AF:

0.000291

AC:

AN:

3454

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

0.074

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.52

CADD

Benign

8.3

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.016

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.59

M_CAP

Pathogenic

0.49

MetaRNN

Benign

0.0089

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

0.96

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.26

REVEL

Benign

0.026

Sift

Benign

0.16

Sift4G

Benign

0.27

Polyphen

0.0

Vest4

0.077

MutPred

0.22

Gain of phosphorylation at P28 (P = 0.0087)

MVP

0.22

MPC

0.17

ClinPred

0.016

GERP RS

2.0

PromoterAI

0.078

Neutral

(source)

Varity_R

0.035

gMVP

0.34

Mutation Taster

=97/3

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