rs3783698

chr14-58514384-G-Achr14-58514384-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001329943.3(KIAA0586):c.4429+1757G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 151,844 control chromosomes in the GnomAD database, including 5,470 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (5470 hom., cov: 32)
• Consequence: KIAA0586 NM_001329943.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.701

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0586	NM_001329943.3	c.4429+1757G>A		intron_variant		ENST00000652326.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0586	ENST00000652326.2	c.4429+1757G>A		intron_variant			NM_001329943.3	P4

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40547 AN: 151726 Hom.: 5468 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.255

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.267 AC: 40541 AN: 151844 Hom.: 5470 Cov.: 32 AF XY: 0.268 AC XY: 19915 AN XY: 74200

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.255

Alfa AF: 0.282 Hom.: 3164

Bravo AF: 0.258

Asia WGS AF: 0.333 AC: 1158 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	8.7
Dann	Benign	0.39

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: rs3783698; hg19: chr14-58981102;