rs11554412

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001174150.2(ARL13B):c.1186C>G(p.Pro396Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00716 in 1,612,916 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P396P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0052 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0074 ( 42 hom. )

Consequence

ARL13B
NM_001174150.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 2.16

Publications

12 publications found

Variant links:

Genes affected

ARL13B (HGNC:25419): (ADP ribosylation factor like GTPase 13B) This gene encodes a member of the ADP-ribosylation factor-like family. The encoded protein is a small GTPase that contains both N-terminal and C-terminal guanine nucleotide-binding motifs. This protein is localized in the cilia and plays a role in cilia formation and in maintenance of cilia. Mutations in this gene are the cause of Joubert syndrome 8. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

ARL13B links:

DHFR2 (HGNC:27309): (dihydrofolate reductase 2) Enables dihydrofolate reductase activity and mRNA binding activity. Involved in tetrahydrofolate metabolic process and thymidine biosynthetic process. Located in mitochondrial inner membrane and mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

DHFR2 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=0.008797377).

BP6

Variant 3-94050868-C-G is Benign according to our data. Variant chr3-94050868-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 199197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0052 (792/152194) while in subpopulation NFE AF = 0.00822 (559/67994). AF 95% confidence interval is 0.00766. There are 8 homozygotes in GnomAd4. There are 364 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARL13B	NM_001174150.2 link	c.1186C>G	p.Pro396Ala	missense_variant	Exon 9 of 10	ENST00000394222.8	NP_001167621.1	Q3SXY8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARL13B	ENST00000394222.8 link	c.1186C>G	p.Pro396Ala	missense_variant	Exon 9 of 10	1	NM_001174150.2	ENSP00000377769.3		Q3SXY8-1

Frequencies

GnomAD3 genomes

AF:

0.00522

AC:

794

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00583

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00359

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00822

Gnomad OTH

AF:

0.00767

GnomAD2 exomes

AF:

0.00605

AC:

1518

AN:

250934

AF XY:

0.00616

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00500

Gnomad ASJ exome

AF:

0.00387

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00404

Gnomad NFE exome

AF:

0.00917

Gnomad OTH exome

AF:

0.00719

GnomAD4 exome

AF:

0.00737

AC:

10764

AN:

1460722

Hom.:

Cov.:

AF XY:

0.00726

AC XY:

5276

AN XY:

726684

show subpopulations

African (AFR)

AF:

0.00129

AC:

AN:

33452

American (AMR)

AF:

0.00497

AC:

222

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00452

AC:

118

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39608

South Asian (SAS)

AF:

0.00399

AC:

344

AN:

86242

European-Finnish (FIN)

AF:

0.00513

AC:

271

AN:

52850

Middle Eastern (MID)

AF:

0.00555

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00840

AC:

9343

AN:

1111618

Other (OTH)

AF:

0.00648

AC:

391

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

519

1038

1558

2077

2596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

342

684

1026

1368

1710

<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:

0.00520

AC:

792

AN:

152194

Hom.:

Cov.:

AF XY:

0.00489

AC XY:

364

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.00132

AC:

AN:

41536

American (AMR)

AF:

0.00582

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00353

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00359

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00822

AC:

559

AN:

67994

Other (OTH)

AF:

0.00759

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

117

156

195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00693

Hom.:

Bravo

AF:

0.00519

TwinsUK

AF:

0.0121

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00814

AC:

ExAC

AF:

0.00647

AC:

785

Asia WGS

AF:

0.00231

AC:

AN:

3476

EpiCase

AF:

0.00714

EpiControl

AF:

0.00842

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jul 19, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ARL13B: BP4, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:3

Jul 29, 2014

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 08, 2016

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joubert syndrome 8

Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joubert syndrome 1

Benign:1

May 28, 2019

Mendelics

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

0.16

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.46

.;.;T;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.79

T;T;.;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.0088

T;T;T;T

MetaSVM

Uncertain

-0.10

MutationAssessor

Benign

1.7

.;.;L;L

PhyloP100

2.2

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.5

D;N;N;N

REVEL

Benign

0.20

Sift

Uncertain

0.010

D;D;D;D

Sift4G

Benign

0.24

T;T;T;T

Polyphen

1.0, 0.95

.;D;P;P

Vest4

0.40

MVP

0.83

MPC

0.077

ClinPred

0.030

GERP RS

5.5

Varity_R

0.065

gMVP

0.27

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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