Variant 14-58450673-A-G 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.1056A>G(p.Ser352Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000879 in 1,609,474 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00049 ( 2 hom. )

Consequence

KIAA0586
NM_001329943.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.328

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:

KIAA0586 (HGNC:):

KIAA0586 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 14-58450673-A-G is Benign according to our data. Variant chr14-58450673-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 475437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-58450673-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.328 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0046 (701/152330) while in subpopulation AFR AF= 0.0161 (671/41574). AF 95% confidence interval is 0.0151. There are 3 homozygotes in gnomad4. There are 318 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

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.1056A>G	p.Ser352Ser	synonymous_variant	8/31	ENST00000652326.2	NP_001316872.1	A0A494C171

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0586	ENST00000652326.2 linkuse as main transcript	c.1056A>G	p.Ser352Ser	synonymous_variant	8/31		NM_001329943.3	ENSP00000498929.1		A0A494C171

Frequencies

GnomAD3 genomes

AF:

0.00459

AC:

699

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0161

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00119

AC:

296

AN:

248758

Hom.:

AF XY:

0.000830

AC XY:

112

AN XY:

134964

show subpopulations

Gnomad AFR exome

AF:

0.0170

Gnomad AMR exome

AF:

0.000754

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.000829

GnomAD4 exome

AF:

0.000489

AC:

713

AN:

1457144

Hom.:

Cov.:

AF XY:

0.000394

AC XY:

286

AN XY:

725204

show subpopulations

Gnomad4 AFR exome

AF:

0.0178

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000903

Gnomad4 OTH exome

AF:

0.000930

GnomAD4 genome

AF:

0.00460

AC:

701

AN:

152330

Hom.:

Cov.:

AF XY:

0.00427

AC XY:

318

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0161

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00225

Hom.:

Bravo

AF:

0.00485

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2020	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

8.3

DANN

Benign

0.67

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