Variant 1-198232599-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_133494.3(NEK7):c.19G>C(p.Gly7Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000963 in 1,453,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

NEK7
NM_133494.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.23

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15491652).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK7	NM_133494.3 linkuse as main transcript	c.19G>C	p.Gly7Arg	missense_variant	2/10	ENST00000367385.9	NP_598001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEK7	ENST00000367385.9 linkuse as main transcript	c.19G>C	p.Gly7Arg	missense_variant	2/10	5	NM_133494.3	ENSP00000356355	P1	Q8TDX7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

250786

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135550

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:

0.0000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000963

AC:

AN:

1453870

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

723814

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000814

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

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

Dec 02, 2021

The c.19G>C (p.G7R) alteration is located in exon 2 (coding exon 1) of the NEK7 gene. This alteration results from a G to C substitution at nucleotide position 19, causing the glycine (G) at amino acid position 7 to be replaced by an arginine (R). 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

Benign

0.25

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.095

T;T;T;.;.;.

Eigen

Benign

0.072

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.93

.;D;D;D;D;D

M_CAP

Benign

0.072

MetaRNN

Benign

0.15

T;T;T;T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

0.55

N;.;N;N;.;.

MutationTaster

Benign

0.97

D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.58

N;D;N;N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0040

D;.;D;D;D;D

Sift4G

Uncertain

0.0050

D;D;D;D;D;D

Polyphen

0.50

P;.;P;.;.;.

Vest4

0.57

MutPred

0.24

Gain of solvent accessibility (P = 0.0306);Gain of solvent accessibility (P = 0.0306);Gain of solvent accessibility (P = 0.0306);Gain of solvent accessibility (P = 0.0306);Gain of solvent accessibility (P = 0.0306);Gain of solvent accessibility (P = 0.0306);

MVP

0.53

MPC

0.74

ClinPred

0.23

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.50

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