Variant 14-75084551-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033116.6(NEK9):c.*13G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 152,346 control chromosomes in the GnomAD database, including 74,204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 74204 hom., cov: 32)

Exomes 𝑓: 1.0 ( 728886 hom. )

Failed GnomAD Quality Control

Consequence

NEK9
NM_033116.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.70

Variant links:

Genes affected

NEK9 (HGNC:18591): (NIMA related kinase 9) This gene encodes a member of the NimA (never in mitosis A) family of serine/threonine protein kinases. The encoded protein is activated in mitosis and, in turn, activates other family members during mitosis. This protein also mediates cellular processes that are essential for interphase progression. [provided by RefSeq, Jul 2016]

NEK9 links:

NEK9 (HGNC:):

NEK9 links:

ZC2HC1C (HGNC:20354): (zinc finger C2HC-type containing 1C) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ZC2HC1C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 14-75084551-C-T is Benign according to our data. Variant chr14-75084551-C-T is described in ClinVar as [Benign]. Clinvar id is 1325899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK9	NM_033116.6 linkuse as main transcript	c.*13G>A		3_prime_UTR_variant	22/22	ENST00000238616.10	NP_149107.4	Q8TD19Q6PKF2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEK9	ENST00000238616 linkuse as main transcript	c.*13G>A		3_prime_UTR_variant	22/22	1	NM_033116.6	ENSP00000238616.5		Q8TD19

Frequencies

GnomAD3 genomes

AF:

0.987

AC:

150223

AN:

152228

Hom.:

74146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.954

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.995

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.994

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.987

GnomAD3 exomes

AF:

0.997

AC:

250556

AN:

251396

Hom.:

124876

AF XY:

0.998

AC XY:

135531

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.954

Gnomad AMR exome

AF:

0.998

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.998

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.999

AC:

1459700

AN:

1461708

Hom.:

728886

Cov.:

AF XY:

0.999

AC XY:

726309

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.951

Gnomad4 AMR exome

AF:

0.998

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.997

GnomAD4 genome

AF:

0.987

AC:

150340

AN:

152346

Hom.:

74204

Cov.:

AF XY:

0.987

AC XY:

73550

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.954

Gnomad4 AMR

AF:

0.995

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.987

Alfa

AF:

0.994

Hom.:

19961

Bravo

AF:

0.984

Asia WGS

AF:

0.998

AC:

3472

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Arthrogryposis, Perthes disease, and upward gaze palsy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

NEK9-related lethal skeletal dysplasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.84

DANN

Benign

0.61

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over