Variant chr13-52072067-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001365552.1(NEK5):c.1726A>G(p.Met576Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0035 in 1,610,050 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0036 ( 10 hom. )

Consequence

NEK5
NM_001365552.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.41

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004542917).

BP6

Variant 13-52072067-T-C is Benign according to our data. Variant chr13-52072067-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2643825.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK5	NM_001365552.1 linkuse as main transcript	c.1726A>G	p.Met576Val	missense_variant	20/24	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.1726A>G	p.Met576Val	missense_variant	20/24		NM_001365552.1	ENSP00000509632.1		A0A8I5KQI9

Frequencies

GnomAD3 genomes

AF:

0.00251

AC:

382

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00424

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00423

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00259

AC:

645

AN:

248956

Hom.:

AF XY:

0.00271

AC XY:

365

AN XY:

134628

show subpopulations

Gnomad AFR exome

AF:

0.000685

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000166

Gnomad FIN exome

AF:

0.00371

Gnomad NFE exome

AF:

0.00430

Gnomad OTH exome

AF:

0.00280

GnomAD4 exome

AF:

0.00361

AC:

5257

AN:

1457704

Hom.:

Cov.:

AF XY:

0.00357

AC XY:

2591

AN XY:

725310

show subpopulations

Gnomad4 AFR exome

AF:

0.000690

Gnomad4 AMR exome

AF:

0.00136

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000163

Gnomad4 FIN exome

AF:

0.00371

Gnomad4 NFE exome

AF:

0.00433

Gnomad4 OTH exome

AF:

0.00252

GnomAD4 genome

AF:

0.00251

AC:

382

AN:

152346

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

182

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000649

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00424

Gnomad4 NFE

AF:

0.00423

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00392

Hom.:

Bravo

AF:

0.00233

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00419

AC:

ExAC

AF:

0.00272

AC:

330

EpiCase

AF:

0.00475

EpiControl

AF:

0.00369

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

NEK5: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.074

DANN

Benign

0.32

DEOGEN2

Benign

0.015

.;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.47

T;.;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.0045

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.17

.;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.46

.;N;.

REVEL

Benign

0.077

Sift

Benign

1.0

.;T;.

Sift4G

Benign

0.75

.;T;T

Polyphen

0.0

.;B;B

Vest4

0.036, 0.038

MVP

0.28

MPC

0.060

ClinPred

0.00080

GERP RS

-1.5

Varity_R

0.047

gMVP

0.038

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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