Variant chr16-2148976-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014353.5(RAB26):c.193A>C(p.Lys65Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000891 in 1,122,338 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.9e-7 ( 0 hom. )

Consequence

RAB26
NM_014353.5 missense, splice_region

Scores

Splicing: ADA: 0.001599

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB26	NM_014353.5 link	c.193A>C	p.Lys65Gln	missense_variant, splice_region_variant	1/9	ENST00000210187.11	NP_055168.2	Q9ULW5-1
RAB26	NM_001308053.1 link	c.-6A>C		splice_region_variant	2/10		NP_001294982.1	Q9ULW5-2
RAB26	NM_001308053.1 link	c.-6A>C		5_prime_UTR_variant	2/10		NP_001294982.1	Q9ULW5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB26	ENST00000210187.11 link	c.193A>C	p.Lys65Gln	missense_variant, splice_region_variant	1/9	1	NM_014353.5	ENSP00000210187.6		Q9ULW5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.91e-7

AC:

AN:

1122338

Hom.:

Cov.:

AF XY:

0.00000187

AC XY:

AN XY:

535866

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.0000222

GnomAD4 genome

Cov.:

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

May 23, 2023

The c.193A>C (p.K65Q) alteration is located in exon 1 (coding exon 1) of the RAB26 gene. This alteration results from a A to C substitution at nucleotide position 193, causing the lysine (K) at amino acid position 65 to be replaced by a glutamine (Q). 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

0.87

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Benign

0.92

DEOGEN2

Benign

0.38

Eigen

Benign

-0.091

Eigen_PC

Benign

-0.10

FATHMM_MKL

Benign

0.46

LIST_S2

Uncertain

0.89

M_CAP

Pathogenic

0.77

MetaRNN

Uncertain

0.74

MetaSVM

Uncertain

-0.093

MutationAssessor

Uncertain

2.9

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.64

Sift

Benign

0.033

Sift4G

Uncertain

0.050

Polyphen

0.12

Vest4

0.57

MutPred

0.70

Loss of methylation at K65 (P = 6e-04);

MVP

0.78

MPC

0.13

ClinPred

0.87

GERP RS

2.7

Varity_R

0.36

gMVP

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0016

dbscSNV1_RF

Benign

0.0080

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over