rs1040461

Positions:

chr6-57190556-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016277.5(RAB23):c.619G>A(p.Gly207Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0867 in 1,613,576 control chromosomes in the GnomAD database, including 7,009 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1220 hom., cov: 32)

Exomes 𝑓: 0.084 ( 5789 hom. )

Consequence

RAB23
NM_016277.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 3.99

Variant links:

Genes affected

RAB23 (HGNC:14263): (RAB23, member RAS oncogene family) This gene encodes a small GTPase of the Ras superfamily. Rab proteins are involved in the regulation of diverse cellular functions associated with intracellular membrane trafficking, including autophagy and immune response to bacterial infection. The encoded protein may play a role in central nervous system development by antagonizing sonic hedgehog signaling. Disruption of this gene has been implicated in Carpenter syndrome as well as cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

RAB23 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012622476).

BP6

Variant 6-57190556-C-T is Benign according to our data. Variant chr6-57190556-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 357640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB23	NM_016277.5 linkuse as main transcript	c.619G>A	p.Gly207Ser	missense_variant	7/7	ENST00000468148.6	NP_057361.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB23	ENST00000468148.6 linkuse as main transcript	c.619G>A	p.Gly207Ser	missense_variant	7/7	1	NM_016277.5	ENSP00000417610	P1
RAB23	ENST00000317483.4 linkuse as main transcript	c.619G>A	p.Gly207Ser	missense_variant	7/7	1		ENSP00000320413	P1

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17523

AN:

152020

Hom.:

1217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.0868

Gnomad ASJ

AF:

0.0377

Gnomad EAS

AF:

0.0951

Gnomad SAS

AF:

0.0798

Gnomad FIN

AF:

0.172

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0825

Gnomad OTH

AF:

0.0931

GnomAD3 exomes

AF:

0.0983

AC:

24708

AN:

251284

Hom.:

1455

AF XY:

0.0948

AC XY:

12873

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.182

Gnomad AMR exome

AF:

0.111

Gnomad ASJ exome

AF:

0.0370

Gnomad EAS exome

AF:

0.0950

Gnomad SAS exome

AF:

0.0794

Gnomad FIN exome

AF:

0.168

Gnomad NFE exome

AF:

0.0811

Gnomad OTH exome

AF:

0.0828

GnomAD4 exome

AF:

0.0837

AC:

122294

AN:

1461438

Hom.:

5789

Cov.:

AF XY:

0.0829

AC XY:

60244

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.177

Gnomad4 AMR exome

AF:

0.110

Gnomad4 ASJ exome

AF:

0.0361

Gnomad4 EAS exome

AF:

0.0669

Gnomad4 SAS exome

AF:

0.0764

Gnomad4 FIN exome

AF:

0.156

Gnomad4 NFE exome

AF:

0.0789

Gnomad4 OTH exome

AF:

0.0831

GnomAD4 genome

AF:

0.115

AC:

17558

AN:

152138

Hom.:

1220

Cov.:

AF XY:

0.116

AC XY:

8649

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.182

Gnomad4 AMR

AF:

0.0871

Gnomad4 ASJ

AF:

0.0377

Gnomad4 EAS

AF:

0.0953

Gnomad4 SAS

AF:

0.0797

Gnomad4 FIN

AF:

0.172

Gnomad4 NFE

AF:

0.0825

Gnomad4 OTH

AF:

0.0936

Alfa

AF:

0.0810

Hom.:

1372

Bravo

AF:

0.112

TwinsUK

AF:

0.0806

AC:

299

ALSPAC

AF:

0.0794

AC:

306

ESP6500AA

AF:

0.183

AC:

806

ESP6500EA

AF:

0.0802

AC:

690

ExAC

AF:

0.0979

AC:

11887

Asia WGS

AF:

0.111

AC:

384

AN:

3478

EpiCase

AF:

0.0740

EpiControl

AF:

0.0697

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Carpenter syndrome

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	This variant is associated with the following publications: (PMID: 29416296) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

RAB23-related Carpenter syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 21, 2019	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Dec 03, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.041

T;T

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.15

T;.

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.69

N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.11

N;N

REVEL

Benign

0.16

Sift

Benign

1.0

T;T

Sift4G

Benign

0.56

T;T

Polyphen

0.0

B;B

Vest4

0.049

MPC

0.18

ClinPred

0.018

GERP RS

5.8

Varity_R

0.097

gMVP

0.23

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