rs3783697

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001329943.3(KIAA0586):c.3920A>G(p.Asp1307Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00616 in 1,550,530 control chromosomes in the GnomAD database, including 407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0092 ( 40 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 367 hom. )

Consequence

KIAA0586
NM_001329943.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.00

Publications

9 publications found

Variant links:

Genes affected

KIAA0586 (HGNC:19960): (KIAA0586) This gene encodes a conserved centrosomal protein that functions in ciliogenesis and responds to hedgehog signaling. Mutations in this gene causes Joubert syndrome 23. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Aug 2016]

KIAA0586 Gene-Disease associations (from GenCC):

Joubert syndrome 23
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
short-rib thoracic dysplasia 14 with polydactyly
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
Joubert syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Joubert syndrome with Jeune asphyxiating thoracic dystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

KIAA0586 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=0.002554804).

BP6

Variant 14-58492205-A-G is Benign according to our data. Variant chr14-58492205-A-G is described in ClinVar as Benign. ClinVar VariationId is 475450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0875 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001329943.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KIAA0586	NM_001329943.3	MANE Select	c.3920A>G	p.Asp1307Gly	missense	Exon 26 of 31	NP_001316872.1
KIAA0586	NM_001244189.2		c.4079A>G	p.Asp1360Gly	missense	Exon 28 of 34	NP_001231118.1
KIAA0586	NM_001329944.2		c.3920A>G	p.Asp1307Gly	missense	Exon 26 of 32	NP_001316873.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KIAA0586	ENST00000652326.2	MANE Select	c.3920A>G	p.Asp1307Gly	missense	Exon 26 of 31	ENSP00000498929.1
KIAA0586	ENST00000619416.4	TSL:1	c.3875A>G	p.Asp1292Gly	missense	Exon 27 of 32	ENSP00000478083.1
KIAA0586	ENST00000423743.7	TSL:1	c.3788A>G	p.Asp1263Gly	missense	Exon 27 of 32	ENSP00000399427.3

Frequencies

GnomAD3 genomes

AF:

0.00925

AC:

1408

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0475

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.0944

Gnomad SAS

AF:

0.00765

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.0162

GnomAD2 exomes

AF:

0.0243

AC:

3839

AN:

157738

AF XY:

0.0209

show subpopulations

Gnomad AFR exome

AF:

0.00171

Gnomad AMR exome

AF:

0.102

Gnomad ASJ exome

AF:

0.00411

Gnomad EAS exome

AF:

0.0949

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000589

Gnomad OTH exome

AF:

0.0132

GnomAD4 exome

AF:

0.00583

AC:

8147

AN:

1398192

Hom.:

367

Cov.:

AF XY:

0.00559

AC XY:

3857

AN XY:

689646

show subpopulations

African (AFR)

AF:

0.000919

AC:

AN:

31572

American (AMR)

AF:

0.0918

AC:

3263

AN:

35558

Ashkenazi Jewish (ASJ)

AF:

0.00397

AC:

100

AN:

25168

East Asian (EAS)

AF:

0.0961

AC:

3423

AN:

35636

South Asian (SAS)

AF:

0.00483

AC:

382

AN:

79072

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49244

Middle Eastern (MID)

AF:

0.00105

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.000400

AC:

431

AN:

1078326

Other (OTH)

AF:

0.00886

AC:

513

AN:

57926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

326

652

977

1303

1629

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

208

312

416

520

<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:

0.00924

AC:

1407

AN:

152338

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

777

AN XY:

74514

show subpopulations

African (AFR)

AF:

0.00168

AC:

AN:

41576

American (AMR)

AF:

0.0474

AC:

726

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3470

East Asian (EAS)

AF:

0.0944

AC:

490

AN:

5190

South Asian (SAS)

AF:

0.00766

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000485

AC:

AN:

68024

Other (OTH)

AF:

0.0161

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

128

193

257

321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00605

Hom.:

Bravo

AF:

0.0159

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000720

AC:

ESP6500EA

AF:

0.000973

AC:

ExAC

AF:

0.00684

AC:

577

Asia WGS

AF:

0.0380

AC:

132

AN:

3476

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Joubert syndrome 23;C4225286:Short-rib thoracic dysplasia 14 with polydactyly (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

MetaRNN

Benign

0.0026

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.5

PhyloP100

7.0

PrimateAI

Benign

0.32

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.28

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.0090

Polyphen

0.96

Vest4

0.31

MPC

0.12

ClinPred

0.025

GERP RS

5.1

Varity_R

0.39

gMVP

0.33

Mutation Taster

=96/4

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over