Genetic Variant NM_014353.5:c.509T>C (chr16-2152860-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V170M) has been classified 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

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:

SNHG19 (HGNC:49574): (small nucleolar RNA host gene 19)

SNHG19 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.509T>C	p.Val170Ala	missense	Exon 6 of 9	NP_055168.2
	RAB26	NM_001308053.1		c.311T>C	p.Val104Ala	missense	Exon 7 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.509T>C	p.Val170Ala	missense	Exon 6 of 9	ENSP00000210187.6	Q9ULW5-1
RAB26	ENST00000541451.5	TSL:1	c.311T>C	p.Val104Ala	missense	Exon 7 of 10	ENSP00000441580.1	Q9ULW5-2
RAB26	ENST00000564426.5	TSL:1	n.739T>C		non_coding_transcript_exon	Exon 8 of 9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000816

AC:

AN:

245140

AF XY:

0.0000150

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 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

African (AFR)

AF:

0.00

AC:

AN:

33268

American (AMR)

AF:

0.0000228

AC:

AN:

43838

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25984

East Asian (EAS)

AF:

0.00

AC:

AN:

39594

South Asian (SAS)

AF:

0.00

AC:

AN:

85642

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52094

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5552

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109322

Other (OTH)

AF:

0.0000166

AC:

AN:

60124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

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

Cov.:

ExAC

AF:

0.00000825

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

0.23

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.020

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.54

Eigen

Benign

0.18

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.72

MetaSVM

Uncertain

-0.28

MutationAssessor

Benign

1.1

PhyloP100

2.9

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.8

REVEL

Pathogenic

0.76

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.030

Polyphen

0.97

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

PromoterAI

-0.040

Neutral

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over