Variant chr14-58442717-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001329943.3(KIAA0586):c.422T>C(p.Met141Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00673 in 1,567,602 control chromosomes in the GnomAD database, including 54 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0069 ( 51 hom. )

Consequence

KIAA0586
NM_001329943.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.497

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061211884).

BP6

Variant 14-58442717-T-C is Benign according to our data. Variant chr14-58442717-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 377258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0586	NM_001329943.3 linkuse as main transcript	c.422T>C	p.Met141Thr	missense_variant	5/31	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.422T>C	p.Met141Thr	missense_variant	5/31		NM_001329943.3	ENSP00000498929	P4

Frequencies

GnomAD3 genomes

AF:

0.00519

AC:

790

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00426

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00481

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00810

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00509

AC:

939

AN:

184644

Hom.:

AF XY:

0.00490

AC XY:

482

AN XY:

98274

show subpopulations

Gnomad AFR exome

AF:

0.00136

Gnomad AMR exome

AF:

0.00289

Gnomad ASJ exome

AF:

0.00956

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00162

Gnomad FIN exome

AF:

0.00519

Gnomad NFE exome

AF:

0.00765

Gnomad OTH exome

AF:

0.00750

GnomAD4 exome

AF:

0.00690

AC:

9766

AN:

1415288

Hom.:

Cov.:

AF XY:

0.00682

AC XY:

4774

AN XY:

699890

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00349

Gnomad4 ASJ exome

AF:

0.0108

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00137

Gnomad4 FIN exome

AF:

0.00617

Gnomad4 NFE exome

AF:

0.00786

Gnomad4 OTH exome

AF:

0.00603

GnomAD4 genome

AF:

0.00519

AC:

790

AN:

152314

Hom.:

Cov.:

AF XY:

0.00458

AC XY:

341

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00425

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00481

Gnomad4 NFE

AF:

0.00810

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00729

Hom.:

Bravo

AF:

0.00484

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00769

AC:

ExAC

AF:

0.00424

AC:

506

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	KIAA0586: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jan 24, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 21, 2019	- -

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 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.023

.;.;T;T;.;T;T;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.65

T;T;T;T;.;T;T;T

MetaRNN

Benign

0.0061

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

.;.;.;L;.;.;.;.

MutationTaster

Benign

0.99

N;N;N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.5

N;.;.;.;N;N;N;N

REVEL

Benign

0.035

Sift

Benign

0.14

T;.;.;.;T;T;T;T

Sift4G

Benign

0.18

T;T;T;T;T;T;T;T

Polyphen

0.0030

.;.;.;B;.;.;.;.

Vest4

0.32

MVP

0.42

MPC

0.036

ClinPred

0.0049

GERP RS

1.3

Varity_R

0.090

gMVP

0.035

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