Variant rs45568037 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001329943.3(KIAA0586):c.4560G>A(p.Pro1520=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,613,662 control chromosomes in the GnomAD database, including 204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 25 hom., cov: 32)

Exomes 𝑓: 0.013 ( 179 hom. )

Consequence

KIAA0586
NM_001329943.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.386

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026349127).

BP6

Variant 14-58547845-G-A is Benign according to our data. Variant chr14-58547845-G-A is described in ClinVar as [Benign]. Clinvar id is 475454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.386 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0121 (1843/152230) while in subpopulation NFE AF= 0.02 (1360/68006). AF 95% confidence interval is 0.0191. There are 25 homozygotes in gnomad4. There are 864 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0586	NM_001329943.3 linkuse as main transcript	c.4560G>A	p.Pro1520=	synonymous_variant	31/31	ENST00000652326.2	NP_001316872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0586	ENST00000652326.2 linkuse as main transcript	c.4560G>A	p.Pro1520=	synonymous_variant	31/31		NM_001329943.3	ENSP00000498929	P4

Frequencies

GnomAD3 genomes

AF:

0.0121

AC:

1844

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00635

Gnomad ASJ

AF:

0.0253

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.0169

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0200

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.0108

AC:

2674

AN:

248598

Hom.:

AF XY:

0.0108

AC XY:

1460

AN XY:

134848

show subpopulations

Gnomad AFR exome

AF:

0.00200

Gnomad AMR exome

AF:

0.00281

Gnomad ASJ exome

AF:

0.0219

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00310

Gnomad FIN exome

AF:

0.0158

Gnomad NFE exome

AF:

0.0163

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.0130

AC:

19003

AN:

1461432

Hom.:

179

Cov.:

AF XY:

0.0131

AC XY:

9530

AN XY:

727010

show subpopulations

Gnomad4 AFR exome

AF:

0.00170

Gnomad4 AMR exome

AF:

0.00311

Gnomad4 ASJ exome

AF:

0.0238

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00326

Gnomad4 FIN exome

AF:

0.0180

Gnomad4 NFE exome

AF:

0.0146

Gnomad4 OTH exome

AF:

0.0118

GnomAD4 genome

AF:

0.0121

AC:

1843

AN:

152230

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

864

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00197

Gnomad4 AMR

AF:

0.00635

Gnomad4 ASJ

AF:

0.0253

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.0169

Gnomad4 NFE

AF:

0.0200

Gnomad4 OTH

AF:

0.00995

Alfa

AF:

0.0177

Hom.:

Bravo

AF:

0.00936

TwinsUK

AF:

0.0138

AC:

ALSPAC

AF:

0.0174

AC:

ESP6500AA

AF:

0.00217

AC:

ESP6500EA

AF:

0.0141

AC:

119

ExAC

AF:

0.0112

AC:

1351

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 04, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	KIAA0586: BP4, BS1, BS2 -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.6

DANN

Uncertain

0.98

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;D;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.040

REVEL

Benign

0.061

Sift

Pathogenic

0.0

Vest4

0.15

MPC

0.018

ClinPred

0.0053

GERP RS

0.68

gMVP

0.0089

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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