14-58482492-ATTT-ATTTT

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001329943.3(KIAA0586):​c.2945-9dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 1,076,144 control chromosomes in the GnomAD database, including 21 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (9 hom., cov: 31)
  • Exomes 𝑓: 0.043 (12 hom.)
• Consequence: KIAA0586 NM_001329943.3 splice_region, 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-A-AT is Benign according to our data. Variant chr14-58482492-A-AT is described in ClinVar as [Benign]. Clinvar id is 445610.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0111 (1615/146144) while in subpopulation NFE AF= 0.0168 (1109/66106). AF 95% confidence interval is 0.016. There are 9 homozygotes in gnomad4. There are 787 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0586	NM_001329943.3	c.2945-9dupT		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_2945-20insT		intron_variant	Intron 20 of 30		NM_001329943.3	ENSP00000498929.1

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1609 AN: 146090 Hom.: 8 Cov.: 31

Gnomad AFR AF: 0.00373

Gnomad AMI AF: 0.00111

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.00298

Gnomad SAS AF: 0.00305

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.00649

Gnomad NFE AF: 0.0168

Gnomad OTH AF: 0.00801

GnomAD4 exome AF: 0.0433 AC: 40240 AN: 930000 Hom.: 12 Cov.: 0 AF XY: 0.0429 AC XY: 19597 AN XY: 457186

Gnomad4 AFR exome AF: 0.0260

Gnomad4 AMR exome AF: 0.0262

Gnomad4 ASJ exome AF: 0.0385

Gnomad4 EAS exome AF: 0.0165

Gnomad4 SAS exome AF: 0.0328

Gnomad4 FIN exome AF: 0.0315

Gnomad4 NFE exome AF: 0.0468

Gnomad4 OTH exome AF: 0.0398

GnomAD4 genome AF: 0.0111 AC: 1615 AN: 146144 Hom.: 9 Cov.: 31 AF XY: 0.0111 AC XY: 787 AN XY: 71064

Gnomad4 AFR AF: 0.00375

Gnomad4 AMR AF: 0.00759

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.00298

Gnomad4 SAS AF: 0.00328

Gnomad4 FIN AF: 0.0136

Gnomad4 NFE AF: 0.0168

Gnomad4 OTH AF: 0.00991

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 17, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

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;