Variant 15-55224004-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The ENST00000336787.6(RAB27A):c.352C>A(p.Gln118Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

RAB27A
ENST00000336787.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.88

Variant links:

Genes affected

RAB27A (HGNC:9766): (RAB27A, member RAS oncogene family) The protein encoded by this gene belongs to the small GTPase superfamily, Rab family. The protein is membrane-bound and may be involved in protein transport and small GTPase mediated signal transduction. Mutations in this gene are associated with Griscelli syndrome type 2. Alternative splicing occurs at this locus and four transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

RAB27A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1

In a chain Ras-related protein Rab-27A (size 219) in uniprot entity RB27A_HUMAN there are 23 pathogenic changes around while only 8 benign (74%) in ENST00000336787.6

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30423757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB27A	NM_183235.3 linkuse as main transcript	c.352C>A	p.Gln118Lys	missense_variant	6/7	ENST00000336787.6	NP_899058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB27A	ENST00000336787.6 linkuse as main transcript	c.352C>A	p.Gln118Lys	missense_variant	6/7	1	NM_183235.3	ENSP00000337761	P1	P51159-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251234

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.02e-7

AC:

AN:

1424198

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

710294

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

0.050

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.27

T;T;T;T;T;.;.

Eigen

Benign

-0.10

Eigen_PC

Benign

0.18

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

.;D;.;.;D;D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.30

T;T;T;T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

-0.040

N;N;N;N;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.11

N;N;N;N;N;N;N

REVEL

Uncertain

0.35

Sift

Benign

1.0

T;T;T;T;T;T;T

Sift4G

Benign

0.95

T;T;T;T;.;.;T

Polyphen

0.058

B;B;B;B;.;.;.

Vest4

0.86

MutPred

0.45

Gain of ubiquitination at Q118 (P = 0.0289);Gain of ubiquitination at Q118 (P = 0.0289);Gain of ubiquitination at Q118 (P = 0.0289);Gain of ubiquitination at Q118 (P = 0.0289);Gain of ubiquitination at Q118 (P = 0.0289);Gain of ubiquitination at Q118 (P = 0.0289);Gain of ubiquitination at Q118 (P = 0.0289);

MVP

0.51

MPC

0.15

ClinPred

0.54

GERP RS

5.7

Varity_R

0.34

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over