Variant chr14-58428196-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001329943.3(KIAA0586):c.-69C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 1,535,014 control chromosomes in the GnomAD database, including 187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 7 hom., cov: 32)

Exomes 𝑓: 0.015 ( 180 hom. )

Consequence

KIAA0586
NM_001329943.3 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.176

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 14-58428196-C-T is Benign according to our data. Variant chr14-58428196-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1188490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0103 (1571/152234) while in subpopulation NFE AF= 0.0168 (1146/68014). AF 95% confidence interval is 0.016. There are 7 homozygotes in gnomad4. There are 728 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0586	NM_001329943.3 linkuse as main transcript	c.-69C>T		5_prime_UTR_variant	1/31	ENST00000652326.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0586	ENST00000652326.2 linkuse as main transcript	c.-69C>T		5_prime_UTR_variant	1/31		NM_001329943.3	P4

Frequencies

GnomAD3 genomes

AF:

0.0103

AC:

1571

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00261

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00969

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.0129

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0168

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00976

AC:

1527

AN:

156464

Hom.:

AF XY:

0.00978

AC XY:

814

AN XY:

83198

show subpopulations

Gnomad AFR exome

AF:

0.00229

Gnomad AMR exome

AF:

0.00534

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00325

Gnomad FIN exome

AF:

0.0123

Gnomad NFE exome

AF:

0.0159

Gnomad OTH exome

AF:

0.00915

GnomAD4 exome

AF:

0.0149

AC:

20665

AN:

1382780

Hom.:

180

Cov.:

AF XY:

0.0144

AC XY:

9839

AN XY:

681514

show subpopulations

Gnomad4 AFR exome

AF:

0.00240

Gnomad4 AMR exome

AF:

0.00528

Gnomad4 ASJ exome

AF:

0.000128

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00374

Gnomad4 FIN exome

AF:

0.0113

Gnomad4 NFE exome

AF:

0.0176

Gnomad4 OTH exome

AF:

0.0118

GnomAD4 genome

AF:

0.0103

AC:

1571

AN:

152234

Hom.:

Cov.:

AF XY:

0.00978

AC XY:

728

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00260

Gnomad4 AMR

AF:

0.00968

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00331

Gnomad4 FIN

AF:

0.0129

Gnomad4 NFE

AF:

0.0168

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00761

Hom.:

Bravo

AF:

0.00952

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.9

DANN

Benign

0.63

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