Genetic Variant RAB26:p.Pro15Ser (chr16-2148826-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.43C>T(p.Pro15Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RAB26
NM_014353.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.417

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=0.23624504).

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.43C>T	p.Pro15Ser	missense	Exon 1 of 9	NP_055168.2
	RAB26	NM_001308053.1		c.-156C>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.43C>T	p.Pro15Ser	missense	Exon 1 of 9	ENSP00000210187.6	Q9ULW5-1
RAB26	ENST00000541451.5	TSL:1	c.-156C>T		5_prime_UTR	Exon 2 of 10	ENSP00000441580.1	Q9ULW5-2
RAB26	ENST00000564426.5	TSL:1	n.87C>T		non_coding_transcript_exon	Exon 2 of 9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1263632

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

622104

African (AFR)

AF:

0.00

AC:

AN:

25240

American (AMR)

AF:

0.00

AC:

AN:

19404

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20436

East Asian (EAS)

AF:

0.00

AC:

AN:

28338

South Asian (SAS)

AF:

0.00

AC:

AN:

59880

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1017910

Other (OTH)

AF:

0.00

AC:

AN:

51276

GnomAD4 genome

Cov.:

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

0.069

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.019

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.69

M_CAP

Pathogenic

0.81

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.0

PhyloP100

0.42

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.51

REVEL

Benign

0.038

Sift

Benign

0.097

Sift4G

Benign

0.20

Polyphen

0.018

Vest4

0.23

MutPred

0.20

Gain of phosphorylation at P15 (P = 0.0218)

MVP

0.56

MPC

0.12

ClinPred

0.056

GERP RS

2.7

PromoterAI

0.028

Neutral

(source)

Varity_R

0.061

gMVP

0.52

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over