rs886039806

Positions:

• chr14-58467887-T-A
• chr14-58467887-T-C
• chr14-58467887-T-G

Variant summary

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

The NM_001329943.3(KIAA0586):​c.2407T>A​(p.Ser803Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIAA0586 NM_001329943.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.43

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/exons	MANE	Protein	UniProt
KIAA0586	NM_001329943.3	c.2407T>A	p.Ser803Thr	missense_variant	16/31	ENST00000652326.2	NP_001316872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0586	ENST00000652326.2	c.2407T>A	p.Ser803Thr	missense_variant	16/31		NM_001329943.3	ENSP00000498929	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460084 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726368

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.000240 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	.;.;T;T;.;.
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.82	T;T;T;T;.;T
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.43	T;T;T;T;T;T
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Uncertain	2.4	.;.;.;M;.;.
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.1	N;.;.;.;N;N
REVEL	Benign	0.17
Sift	Uncertain	0.0040	D;.;.;.;D;D
Sift4G	Uncertain	0.012	D;D;D;D;D;D
Polyphen		1.0	.;.;.;D;.;.
Vest4		0.50
MutPred		0.21		.;.;.;Gain of catalytic residue at P793 (P = 0);.;.;
MVP		0.82
MPC		0.16
ClinPred		0.94	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.38
gMVP		0.30

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: rs886039806; hg19: chr14-58934605;