Variant chr1-198278060-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_133494.3(NEK7):c.472A>T(p.Met158Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000219 in 1,369,088 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

NEK7
NM_133494.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.82

Variant links:

Genes affected

NEK7 (HGNC:13386): (NIMA related kinase 7) NIMA-related kinases share high amino acid sequence identity with the gene product of the Aspergillus nidulans 'never in mitosis A' gene, which controls initiation of mitosis.[supplied by OMIM, Jul 2002]

NEK7 links:

NEK7 (HGNC:):

NEK7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
NEK7	NM_133494.3 linkuse as main transcript	c.472A>T	p.Met158Leu	missense_variant	6/10	ENST00000367385.9	NP_598001.1	Q8TDX7-1B2R8K8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NEK7	ENST00000367385.9 linkuse as main transcript	c.472A>T	p.Met158Leu	missense_variant	6/10	5	NM_133494.3	ENSP00000356355.4	Q8TDX7-1
NEK7	ENST00000538004.5 linkuse as main transcript	c.472A>T	p.Met158Leu	missense_variant	6/10	1		ENSP00000444621.1	Q8TDX7-1
NEK7	ENST00000493790.1 linkuse as main transcript	n.357A>T		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000807

AC:

AN:

247734

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133858

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000219

AC:

AN:

1369088

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

686254

show subpopulations

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:

0.00000291

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 13, 2024

The c.472A>T (p.M158L) alteration is located in exon 6 (coding exon 5) of the NEK7 gene. This alteration results from a A to T substitution at nucleotide position 472, causing the methionine (M) at amino acid position 158 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.22

T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

0.017

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

.;D

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.65

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

N;N

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.24

Sift

Benign

0.28

T;T

Sift4G

Benign

0.71

T;T

Polyphen

0.0090

B;B

Vest4

0.61

MutPred

0.63

Loss of methylation at K163 (P = 0.0761);Loss of methylation at K163 (P = 0.0761);

MVP

0.80

MPC

0.64

ClinPred

0.47

GERP RS

5.6

Varity_R

0.64

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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