Variant 13-52065607-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001365552.1(NEK5):c.1852T>C(p.Phe618Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000244 in 1,611,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

NEK5
NM_001365552.1 missense, splice_region

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.36

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031876206).

BP6

Variant 13-52065607-A-G is Benign according to our data. Variant chr13-52065607-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2370163.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK5	NM_001365552.1 linkuse as main transcript	c.1852T>C	p.Phe618Leu	missense_variant, splice_region_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.1852T>C	p.Phe618Leu	missense_variant, splice_region_variant	21/24		NM_001365552.1	ENSP00000509632.1		A0A8I5KQI9

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000100

AC:

AN:

249448

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135006

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:

0.0000463

Gnomad NFE exome

AF:

0.000214

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000254

AC:

370

AN:

1458944

Hom.:

Cov.:

AF XY:

0.000233

AC XY:

169

AN XY:

725750

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

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:

0.0000187

Gnomad4 NFE exome

AF:

0.000305

Gnomad4 OTH exome

AF:

0.000481

GnomAD4 genome

AF:

0.000151

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000253

Hom.:

Bravo

AF:

0.000144

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.68

CADD

Benign

1.3

DANN

Benign

0.61

DEOGEN2

Benign

0.016

.;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0027

LIST_S2

Benign

0.30

T;.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.032

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.49

.;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.97

.;N;.

REVEL

Benign

0.062

Sift

Benign

0.45

.;T;.

Sift4G

Benign

0.61

.;T;T

Polyphen

0.0

.;B;B

Vest4

0.011, 0.052

MutPred

0.28

Gain of catalytic residue at G642 (P = 0.0013);Gain of catalytic residue at G642 (P = 0.0013);Gain of catalytic residue at G642 (P = 0.0013);

MVP

0.34

MPC

0.067

ClinPred

0.015

GERP RS

-2.8

Varity_R

0.050

gMVP

0.11

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