rs9843350

Variant names:

• chr3-27364888-A-G
• rs9843350
• NM_001394966.1:c.-38+4337T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

NEK10 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 44

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NEK10	NM_001394966.1	c.-38+4337T>C		intron_variant	Intron 1 of 35	ENST00000691995.1	NP_001381895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEK10	ENST00000691995.1	c.-38+4337T>C		intron_variant	Intron 1 of 35		NM_001394966.1	ENSP00000509472.1

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

African (AFR) AF: 0.152 AC: 6328 AN: 41520

American (AMR) AF: 0.0374 AC: 573 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 56 AN: 3470

East Asian (EAS) AF: 0.0459 AC: 237 AN: 5168

South Asian (SAS) AF: 0.0205 AC: 99 AN: 4830

European-Finnish (FIN) AF: 0.0124 AC: 132 AN: 10616

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0174 AC: 1181 AN: 68036

Other (OTH) AF: 0.0506 AC: 107 AN: 2114

Alfa AF: 0.0312 Hom.: 195

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
PhyloP100		0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9843350; hg19: chr3-27406379;