14-58482492-ATTT-ATTTTT

Variant names:

• chr14-58482492-A-ATT
• rs748594194
• NM_001329943.3:c.2945-10_2945-9dupTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001329943.3(KIAA0586):​c.2945-10_2945-9dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 987,046 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: KIAA0586 NM_001329943.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0586	NM_001329943.3	c.2945-10_2945-9dupTT		splice_region_variant, 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.2945-21_2945-20insTT		intron_variant	Intron 20 of 30		NM_001329943.3	ENSP00000498929.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.000152 AC: 150 AN: 987046 Hom.: 0 Cov.: 0 AF XY: 0.000159 AC XY: 77 AN XY: 484414

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000250

Gnomad4 ASJ exome AF: 0.000189

Gnomad4 EAS exome AF: 0.0000363

Gnomad4 SAS exome AF: 0.000306

Gnomad4 FIN exome AF: 0.000105

Gnomad4 NFE exome AF: 0.000154

Gnomad4 OTH exome AF: 0.0000743

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BranchPoint Hunter		4.0

Splicing

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;