rs748594194

Variant names:

• chr14-58482492-ATTT-A
• NM_001329943.3:c.2945-11_2945-9delTTT

Your query was ambiguous. Multiple possible variants found:

• chr14-58482492-ATTT-A
• chr14-58482492-ATTT-AT
• chr14-58482492-ATTT-ATT
• chr14-58482492-ATTT-ATTTT
• chr14-58482492-ATTT-ATTTTT
• chr14-58482492-ATTT-ATTTTTT
• chr14-58482492-ATTT-ATTTTTTT

Variant summary

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

The NM_001329943.3(KIAA0586):​c.2945-11_2945-9delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000607 in 988,540 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000061 (0 hom.)
• Consequence: KIAA0586 NM_001329943.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.360

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.2945-11_2945-9delTTT		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.2945-20_2945-18delTTT		intron_variant	Intron 20 of 30		NM_001329943.3	ENSP00000498929.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000607 AC: 6 AN: 988540 Hom.: 0 AF XY: 0.00000618 AC XY: 3 AN XY: 485148

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000631

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000204

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000517

Gnomad4 OTH exome AF: 0.00

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

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-58949210;