Variant chr7-140411976-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001008749.3(RAB19):c.304C>T(p.Arg102Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,614,014 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

RAB19
NM_001008749.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.361

Variant links:

Genes affected

RAB19 (HGNC:19982): (RAB19, member RAS oncogene family) Predicted to enable GTPase activity. Predicted to be involved in autophagosome assembly and intracellular protein transport. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

RAB19 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
RAB19	NM_001008749.3 linkuse as main transcript	c.304C>T	p.Arg102Trp	missense_variant	3/4	ENST00000537763.6	NP_001008749.2	A4D1S5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB19	ENST00000537763.6 linkuse as main transcript	c.304C>T	p.Arg102Trp	missense_variant	3/4	2	NM_001008749.3	ENSP00000440167.1		A4D1S5-1
RAB19	ENST00000356407.3 linkuse as main transcript	c.304C>T	p.Arg102Trp	missense_variant	2/3	1		ENSP00000348778.3		A4D1S5-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251468

Hom.:

AF XY:

0.0000441

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000356

AC:

AN:

1461762

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000369

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000227

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Dec 13, 2022

The c.304C>T (p.R102W) alteration is located in exon 3 (coding exon 2) of the RAB19 gene. This alteration results from a C to T substitution at nucleotide position 304, causing the arginine (R) at amino acid position 102 to be replaced by a tryptophan (W). 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

Benign

0.22

BayesDel_addAF

Benign

-0.054

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.63

.;D;D

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.88

D;D;.

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.69

D;D;D

MetaSVM

Uncertain

0.55

MutationAssessor

Pathogenic

2.9

.;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-6.6

D;D;D

REVEL

Uncertain

0.63

Sift

Uncertain

0.014

D;D;D

Sift4G

Uncertain

0.014

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.42, 0.44

MutPred

0.51

Loss of solvent accessibility (P = 0.0217);Loss of solvent accessibility (P = 0.0217);Loss of solvent accessibility (P = 0.0217);

MVP

0.60

MPC

0.71

ClinPred

0.73

GERP RS

3.6

Varity_R

0.54

gMVP

0.66

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over