rs112062713

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_001174150.2(ARL13B):c.1261A>G(p.Ser421Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000607 in 1,613,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

ARL13B
NM_001174150.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:1

Conservation

PhyloP100: 1.53

Publications

0 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026384115).

BP6

Variant 3-94053237-A-G is Benign according to our data. Variant chr3-94053237-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 405194.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000335 (51/152188) while in subpopulation AFR AF = 0.00118 (49/41456). AF 95% confidence interval is 0.000919. There are 0 homozygotes in GnomAd4. There are 24 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001174150.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARL13B	NM_001174150.2	MANE Select	c.1261A>G	p.Ser421Gly	missense	Exon 10 of 10	NP_001167621.1	Q3SXY8-1
ARL13B	NM_182896.3		c.1261A>G	p.Ser421Gly	missense	Exon 10 of 11	NP_878899.1	Q3SXY8-1
ARL13B	NM_001321328.2		c.1216A>G	p.Ser406Gly	missense	Exon 11 of 11	NP_001308257.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARL13B	ENST00000394222.8	TSL:1 MANE Select	c.1261A>G	p.Ser421Gly	missense	Exon 10 of 10	ENSP00000377769.3	Q3SXY8-1
ARL13B	ENST00000471138.5	TSL:1	c.1261A>G	p.Ser421Gly	missense	Exon 10 of 11	ENSP00000420780.1	Q3SXY8-1
ARL13B	ENST00000535334.5	TSL:1	c.952A>G	p.Ser318Gly	missense	Exon 9 of 9	ENSP00000445145.1	Q3SXY8-3

Frequencies

GnomAD3 genomes

AF:

0.000335

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000717

AC:

AN:

251008

AF XY:

0.0000442

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1461160

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

726906

show subpopulations

African (AFR)

AF:

0.00120

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53060

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111734

Other (OTH)

AF:

0.000116

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000335

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.00118

AC:

AN:

41456

American (AMR)

AF:

0.00

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68034

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000128

Hom.:

Bravo

AF:

0.000427

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Joubert syndrome 8 (2)

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.56

CADD

Benign

8.4

(source)

DANN

Benign

0.54

DEOGEN2

Benign

0.056

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.68

M_CAP

Benign

0.017

MetaRNN

Benign

0.026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

1.5

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.0

REVEL

Benign

0.11

Sift

Benign

0.34

Sift4G

Benign

0.69

Polyphen

0.0010

Vest4

0.094

MVP

0.37

MPC

0.068

ClinPred

0.024

GERP RS

1.1

Varity_R

0.054

gMVP

0.22

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over