Variant 13-52065495-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001365552.1(NEK5):c.1964C>T(p.Thr655Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,613,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

NEK5
NM_001365552.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.34

Variant links:

Genes affected

NEK5 (HGNC:7748): (NIMA related kinase 5) Predicted to enable ATP binding activity; metal ion binding activity; and protein kinase activity. Predicted to be involved in protein phosphorylation. Predicted to act upstream of or within positive regulation of cysteine-type endopeptidase activity and positive regulation of striated muscle cell differentiation. [provided by Alliance of Genome Resources, Apr 2022]

NEK5 links:

NEK5 (HGNC:):

NEK5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.033496857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK5	NM_001365552.1 linkuse as main transcript	c.1964C>T	p.Thr655Met	missense_variant	21/24	ENST00000684899.1	NP_001352481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEK5	ENST00000684899.1 linkuse as main transcript	c.1964C>T	p.Thr655Met	missense_variant	21/24		NM_001365552.1	ENSP00000509632.1		A0A8I5KQI9

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000915

AC:

AN:

251464

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135912

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:

0.000686

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000458

AC:

AN:

1461516

Hom.:

Cov.:

AF XY:

0.0000619

AC XY:

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000557

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000104

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.000115

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jan 04, 2024

The c.2039C>T (p.T680M) alteration is located in exon 22 (coding exon 20) of the NEK5 gene. This alteration results from a C to T substitution at nucleotide position 2039, causing the threonine (T) at amino acid position 680 to be replaced by a methionine (M). 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

0.10

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0089

.;T;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.54

T;.;T

M_CAP

Benign

0.047

MetaRNN

Benign

0.033

T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.2

.;M;M

PrimateAI

Benign

0.31

PROVEAN

Benign

-2.2

.;N;.

REVEL

Benign

0.16

Sift

Pathogenic

0.0

.;D;.

Sift4G

Uncertain

0.013

.;D;D

Polyphen

0.46

.;P;P

Vest4

0.11, 0.22

MVP

0.76

MPC

0.092

ClinPred

0.20

GERP RS

3.3

Varity_R

0.13

gMVP

0.44

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