dbSNP rs11611: KIAA0586:p.Ile1487Ile (chr14-58540102-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001329943.3(KIAA0586):c.4461T>C(p.Ile1487Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00479 in 1,563,672 control chromosomes in the GnomAD database, including 209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 112 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 97 hom. )

Consequence

KIAA0586
NM_001329943.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.927

Publications

4 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 14-58540102-T-C is Benign according to our data. Variant chr14-58540102-T-C is described in ClinVar as Benign. ClinVar VariationId is 475453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.927 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.065 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0586	NM_001329943.3 link	c.4461T>C	p.Ile1487Ile	synonymous_variant	Exon 30 of 31	ENST00000652326.2	NP_001316872.1	A0A494C171

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0586	ENST00000652326.2 link	c.4461T>C	p.Ile1487Ile	synonymous_variant	Exon 30 of 31		NM_001329943.3	ENSP00000498929.1		A0A494C171

Frequencies

GnomAD3 genomes

AF:

0.0201

AC:

3058

AN:

152194

Hom.:

103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0665

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00740

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.0110

Gnomad SAS

AF:

0.00870

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.00705

AC:

1294

AN:

183502

AF XY:

0.00631

show subpopulations

Gnomad AFR exome

AF:

0.0684

Gnomad AMR exome

AF:

0.00409

Gnomad ASJ exome

AF:

0.00302

Gnomad EAS exome

AF:

0.0107

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000619

Gnomad OTH exome

AF:

0.00468

GnomAD4 exome

AF:

0.00311

AC:

4396

AN:

1411360

Hom.:

Cov.:

AF XY:

0.00317

AC XY:

2213

AN XY:

697620

show subpopulations

African (AFR)

AF:

0.0672

AC:

2164

AN:

32184

American (AMR)

AF:

0.00448

AC:

170

AN:

37976

Ashkenazi Jewish (ASJ)

AF:

0.00308

AC:

AN:

25358

East Asian (EAS)

AF:

0.0115

AC:

437

AN:

37848

South Asian (SAS)

AF:

0.00847

AC:

678

AN:

80008

European-Finnish (FIN)

AF:

0.0000198

AC:

AN:

50574

Middle Eastern (MID)

AF:

0.00666

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.000350

AC:

379

AN:

1083136

Other (OTH)

AF:

0.00770

AC:

451

AN:

58570

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

179

358

537

716

895

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<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:

0.0203

AC:

3093

AN:

152312

Hom.:

112

Cov.:

AF XY:

0.0196

AC XY:

1461

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0671

AC:

2788

AN:

41552

American (AMR)

AF:

0.00739

AC:

113

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3468

East Asian (EAS)

AF:

0.0110

AC:

AN:

5192

South Asian (SAS)

AF:

0.00891

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000735

AC:

AN:

68030

Other (OTH)

AF:

0.0128

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

142

284

426

568

710

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.00787

Hom.:

Bravo

AF:

0.0224

Asia WGS

AF:

0.0260

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 25, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.11

(source)

DANN

Benign

0.32

PhyloP100

-0.93

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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