rs9843350

chr3-27364888-A-G

Variant summary

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

The NM_001394966.1(NEK10):c.-38+4337T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0573 in 152,262 control chromosomes in the GnomAD database, including 504 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 0.057 (504 hom., cov: 32)
• Consequence: NEK10 NM_001394966.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225

Genes affected

NEK10 (HGNC:18592): (NIMA related kinase 10) Enables protein kinase activity. Involved in several processes, including mucociliary clearance; positive regulation of protein phosphorylation; and regulation of ERK1 and ERK2 cascade. Part of protein kinase complex. Implicated in primary ciliary dyskinesia 44. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK10	NM_001394966.1	c.-38+4337T>C		intron_variant		ENST00000691995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK10	ENST00000691995.1	c.-38+4337T>C		intron_variant			NM_001394966.1	P1

Frequencies

GnomAD3 genomes AF: 0.0573 AC: 8715 AN: 152144 Hom.: 502 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0375

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.0459

Gnomad SAS AF: 0.0205

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0174

Gnomad OTH AF: 0.0516

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

GnomAD4 genome AF: 0.0573 AC: 8718 AN: 152262 Hom.: 504 Cov.: 32 AF XY: 0.0558 AC XY: 4154 AN XY: 74462

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.0374

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.0459

Gnomad4 SAS AF: 0.0205

Gnomad4 FIN AF: 0.0124

Gnomad4 NFE AF: 0.0174

Gnomad4 OTH AF: 0.0506

Alfa AF: 0.0259 Hom.: 107

Bravo AF: 0.0639

Asia WGS AF: 0.0600 AC: 208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.5
Dann	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9843350; hg19: chr3-27406379;