14-58427859-T-C

Position:

• chr14-58427859-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001329943.3(KIAA0586):​c.-406T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 1,383,130 control chromosomes in the GnomAD database, including 186,448 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19355 hom., cov: 32)
  • Exomes 𝑓: 0.52 (167093 hom.)
• Consequence: KIAA0586 NM_001329943.3 5_prime_UTR
• Scores: Splicing: ADA: 0.00008259
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0860

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]

KIAA0586 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 14-58427859-T-C is Benign according to our data. Variant chr14-58427859-T-C is described in ClinVar as [Benign]. Clinvar id is 1174463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0586	NM_001329943.3	c.-406T>C		5_prime_UTR_variant	1/31	ENST00000652326.2	NP_001316872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0586	ENST00000652326	c.-406T>C		5_prime_UTR_variant	1/31		NM_001329943.3	ENSP00000498929.1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76075 AN: 151888 Hom.: 19351 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.503

GnomAD4 exome AF: 0.518 AC: 638171 AN: 1231124 Hom.: 167093 Cov.: 18 AF XY: 0.520 AC XY: 311733 AN XY: 599000

Gnomad4 AFR exome AF: 0.396

Gnomad4 AMR exome AF: 0.603

Gnomad4 ASJ exome AF: 0.521

Gnomad4 EAS exome AF: 0.441

Gnomad4 SAS exome AF: 0.603

Gnomad4 FIN exome AF: 0.543

Gnomad4 NFE exome AF: 0.516

Gnomad4 OTH exome AF: 0.523

GnomAD4 genome AF: 0.501 AC: 76087 AN: 152006 Hom.: 19355 Cov.: 32 AF XY: 0.504 AC XY: 37449 AN XY: 74296

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.499

Alfa AF: 0.529 Hom.: 28801

Bravo AF: 0.494

Asia WGS AF: 0.523 AC: 1819 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.2
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000083
dbscSNV1_RF	Benign	0.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs3783694; hg19: chr14-58894577;