14-58428196-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001329943.3(KIAA0586):c.-69C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 1,535,014 control chromosomes in the GnomAD database, including 187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (7 hom., cov: 32)
  • Exomes 𝑓: 0.015 (180 hom.)
• Consequence: KIAA0586 NM_001329943.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.176

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 14-58428196-C-T is Benign according to our data. Variant chr14-58428196-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1188490.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0103 (1571/152234) while in subpopulation NFE AF= 0.0168 (1146/68014). AF 95% confidence interval is 0.016. There are 7 homozygotes in gnomad4. There are 728 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0586	NM_001329943.3	c.-69C>T		5_prime_UTR_variant	1/31	ENST00000652326.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0586	ENST00000652326.2	c.-69C>T		5_prime_UTR_variant	1/31		NM_001329943.3	P4

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1571 AN: 152116 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00261

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00969

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.0129

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0168

Gnomad OTH AF: 0.00813

GnomAD3 exomes AF: 0.00976 AC: 1527 AN: 156464 Hom.: 19 AF XY: 0.00978 AC XY: 814 AN XY: 83198

Gnomad AFR exome AF: 0.00229

Gnomad AMR exome AF: 0.00534

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00325

Gnomad FIN exome AF: 0.0123

Gnomad NFE exome AF: 0.0159

Gnomad OTH exome AF: 0.00915

GnomAD4 exome AF: 0.0149 AC: 20665 AN: 1382780 Hom.: 180 Cov.: 32 AF XY: 0.0144 AC XY: 9839 AN XY: 681514

Gnomad4 AFR exome AF: 0.00240

Gnomad4 AMR exome AF: 0.00528

Gnomad4 ASJ exome AF: 0.000128

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00374

Gnomad4 FIN exome AF: 0.0113

Gnomad4 NFE exome AF: 0.0176

Gnomad4 OTH exome AF: 0.0118

GnomAD4 genome AF: 0.0103 AC: 1571 AN: 152234 Hom.: 7 Cov.: 32 AF XY: 0.00978 AC XY: 728 AN XY: 74436

Gnomad4 AFR AF: 0.00260

Gnomad4 AMR AF: 0.00968

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00331

Gnomad4 FIN AF: 0.0129

Gnomad4 NFE AF: 0.0168

Gnomad4 OTH AF: 0.00757

Alfa AF: 0.00761 Hom.: 2

Bravo AF: 0.00952

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	6.9
Dann	Benign	0.63

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: rs145502517; hg19: chr14-58894914;