14-58482492-ATTT-ATT

Variant names:

• chr14-58482492-AT-A
• rs748594194
• NM_001329943.3:c.2945-9delT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001329943.3(KIAA0586):​c.2945-9delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 888,914 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 31)
  • Exomes 𝑓: 0.15 (0 hom.)
• Consequence: KIAA0586 NM_001329943.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0280

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 14-58482492-AT-A is Benign according to our data. Variant chr14-58482492-AT-A is described in ClinVar as [Benign]. Clinvar id is 2934616.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0586	NM_001329943.3	c.2945-9delT		intron_variant	Intron 20 of 30	ENST00000652326.2	NP_001316872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0586	ENST00000652326.2	c.2945-20delT		intron_variant	Intron 20 of 30		NM_001329943.3	ENSP00000498929.1

Frequencies

GnomAD3 genomes AF: 0.00117 AC: 171 AN: 145756 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000451

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000823

Gnomad ASJ AF: 0.000298

Gnomad EAS AF: 0.000198

Gnomad SAS AF: 0.000218

Gnomad FIN AF: 0.00428

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00143

Gnomad OTH AF: 0.00252

GnomAD4 exome AF: 0.152 AC: 113233 AN: 743106 Hom.: 0 Cov.: 0 AF XY: 0.154 AC XY: 56131 AN XY: 364070

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.184

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.204

Gnomad4 SAS exome AF: 0.168

Gnomad4 FIN exome AF: 0.177

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.166

GnomAD4 genome AF: 0.00117 AC: 171 AN: 145808 Hom.: 0 Cov.: 31 AF XY: 0.00117 AC XY: 83 AN XY: 70858

Gnomad4 AFR AF: 0.000450

Gnomad4 AMR AF: 0.000822

Gnomad4 ASJ AF: 0.000298

Gnomad4 EAS AF: 0.000199

Gnomad4 SAS AF: 0.000219

Gnomad4 FIN AF: 0.00428

Gnomad4 NFE AF: 0.00143

Gnomad4 OTH AF: 0.00249

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Joubert syndrome 23;C4225286:Short-rib thoracic dysplasia 14 with polydactyly Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BranchPoint Hunter		4.0

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

Other links and lift over

dbSNP: rs748594194; hg19: chr14-58949210;