rs1040461

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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

Publications

37 publications found

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 Gene-Disease associations (from GenCC):

RAB23-related Carpenter syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, G2P
Carpenter syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

RAB23 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
RAB23	NM_016277.5 link	c.619G>A	p.Gly207Ser	missense_variant	Exon 7 of 7	ENST00000468148.6	NP_057361.3	Q9ULC3A0A024RD41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB23	ENST00000468148.6 link	c.619G>A	p.Gly207Ser	missense_variant	Exon 7 of 7	1	NM_016277.5	ENSP00000417610.1		Q9ULC3
RAB23	ENST00000317483.4 link	c.619G>A	p.Gly207Ser	missense_variant	Exon 7 of 7	1		ENSP00000320413.3		Q9ULC3

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

GnomAD2 exomes

AF:

0.0983

AC:

24708

AN:

251284

AF XY:

0.0948

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 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

African (AFR)

AF:

0.177

AC:

5934

AN:

33466

American (AMR)

AF:

0.110

AC:

4912

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0361

AC:

942

AN:

26130

East Asian (EAS)

AF:

0.0669

AC:

2656

AN:

39684

South Asian (SAS)

AF:

0.0764

AC:

6590

AN:

86250

European-Finnish (FIN)

AF:

0.156

AC:

8348

AN:

53412

Middle Eastern (MID)

AF:

0.0362

AC:

209

AN:

5766

European-Non Finnish (NFE)

AF:

0.0789

AC:

87683

AN:

1111622

Other (OTH)

AF:

0.0831

AC:

5020

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

6284

12568

18853

25137

31421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3232

6464

9696

12928

16160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.115

AC:

17558

AN:

152138

Hom.:

1220

Cov.:

AF XY:

0.116

AC XY:

8649

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.182

AC:

7550

AN:

41500

American (AMR)

AF:

0.0871

AC:

1332

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0377

AC:

131

AN:

3472

East Asian (EAS)

AF:

0.0953

AC:

493

AN:

5174

South Asian (SAS)

AF:

0.0797

AC:

384

AN:

4818

European-Finnish (FIN)

AF:

0.172

AC:

1816

AN:

10554

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0825

AC:

5613

AN:

68000

Other (OTH)

AF:

0.0936

AC:

198

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

766

1533

2299

3066

3832

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0924

Hom.:

3614

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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 29416296) -

RAB23-related Carpenter syndrome

Benign:2

Nov 21, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Dec 03, 2021

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

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

4.0

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over