rs33944211

Variant names:

Variant summary

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

The NM_001174150.2(ARL13B):c.1043C>G(p.Thr348Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,601,378 control chromosomes in the GnomAD database, including 9,697 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 Benign (★★).

Frequency

Genomes: 𝑓 0.081 ( 626 hom., cov: 31)

Exomes 𝑓: 0.11 ( 9071 hom. )

Consequence

ARL13B
NM_001174150.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.254

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016124547).

BP6

Variant 3-94049424-C-G is Benign according to our data. Variant chr3-94049424-C-G is described in ClinVar as [Benign]. Clinvar id is 128452.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-94049424-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARL13B	NM_001174150.2 link	c.1043C>G	p.Thr348Ser	missense_variant	Exon 8 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.1043C>G	p.Thr348Ser	missense_variant	Exon 8 of 10	1	NM_001174150.2	ENSP00000377769.3		Q3SXY8-1

Frequencies

GnomAD3 genomes

AF:

0.0815

AC:

12360

AN:

151572

Hom.:

627

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0199

Gnomad AMI

AF:

0.0374

Gnomad AMR

AF:

0.0719

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.0722

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.0987

Gnomad MID

AF:

0.197

Gnomad NFE

AF:

0.113

Gnomad OTH

AF:

0.0948

GnomAD3 exomes

AF:

0.0980

AC:

24218

AN:

247106

Hom.:

1388

AF XY:

0.104

AC XY:

13880

AN XY:

133542

show subpopulations

Gnomad AFR exome

AF:

0.0188

Gnomad AMR exome

AF:

0.0592

Gnomad ASJ exome

AF:

0.137

Gnomad EAS exome

AF:

0.0718

Gnomad SAS exome

AF:

0.137

Gnomad FIN exome

AF:

0.0964

Gnomad NFE exome

AF:

0.111

Gnomad OTH exome

AF:

0.110

GnomAD4 exome

AF:

0.108

AC:

156405

AN:

1449690

Hom.:

9071

Cov.:

AF XY:

0.109

AC XY:

78802

AN XY:

721102

show subpopulations

Gnomad4 AFR exome

AF:

0.0175

Gnomad4 AMR exome

AF:

0.0628

Gnomad4 ASJ exome

AF:

0.134

Gnomad4 EAS exome

AF:

0.0827

Gnomad4 SAS exome

AF:

0.136

Gnomad4 FIN exome

AF:

0.0964

Gnomad4 NFE exome

AF:

0.110

Gnomad4 OTH exome

AF:

0.114

GnomAD4 genome

AF:

0.0814

AC:

12349

AN:

151688

Hom.:

626

Cov.:

AF XY:

0.0809

AC XY:

5993

AN XY:

74124

show subpopulations

Gnomad4 AFR

AF:

0.0198

Gnomad4 AMR

AF:

0.0720

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.0722

Gnomad4 SAS

AF:

0.126

Gnomad4 FIN

AF:

0.0987

Gnomad4 NFE

AF:

0.113

Gnomad4 OTH

AF:

0.0943

Alfa

AF:

0.109

Hom.:

361

Bravo

AF:

0.0749

TwinsUK

AF:

0.107

AC:

396

ALSPAC

AF:

0.111

AC:

427

ESP6500AA

AF:

0.0222

AC:

ESP6500EA

AF:

0.120

AC:

1033

ExAC

AF:

0.0985

AC:

11957

Asia WGS

AF:

0.0880

AC:

306

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Mar 02, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joubert syndrome 8

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 31, 2017

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: 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:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.050

.;.;T;T

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.094

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.66

T;T;.;T

MetaRNN

Benign

0.0016

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.60

.;.;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.020

N;N;N;N

REVEL

Benign

0.067

Sift

Benign

0.053

T;D;T;T

Sift4G

Benign

0.25

T;T;T;T

Polyphen

0.073, 0.012

.;B;B;B

Vest4

0.12

MutPred

0.13

.;.;Gain of glycosylation at T348 (P = 0.0205);Gain of glycosylation at T348 (P = 0.0205);

MPC

0.067

ClinPred

0.0035

GERP RS

3.0

Varity_R

0.065

gMVP

0.12

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over