Variant chr13-52072053-A-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_001365552.1(NEK5):c.1740T>G(p.Asn580Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,459,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

NEK5
NM_001365552.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.803

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:

ALG11 (HGNC:32456): (ALG11 alpha-1,2-mannosyltransferase) This gene encodes a GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase which is localized to the cytosolic side of the endoplasmic reticulum (ER) and catalyzes the transfer of the fourth and fifth mannose residue from GDP-mannose (GDP-Man) to Man3GlcNAc2-PP-dolichol and Man4GlcNAc2-PP-dolichol resulting in the production of Man5GlcNAc2-PP-dolichol. Mutations in this gene are associated with congenital disorder of glycosylation type Ip (CDGIP). This gene overlaps but is distinct from the UTP14, U3 small nucleolar ribonucleoprotein, homolog C (yeast) gene. A pseudogene of the GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase has been identified on chromosome 19. [provided by RefSeq, Aug 2010]

ALG11 links:

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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=0.25056762).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK5	NM_001365552.1 link	c.1740T>G	p.Asn580Lys	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 link	c.1740T>G	p.Asn580Lys	missense_variant	20/24		NM_001365552.1	ENSP00000509632.1		A0A8I5KQI9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1459292

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726128

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Jul 21, 2021

The c.1815T>G (p.N605K) alteration is located in exon 21 (coding exon 19) of the NEK5 gene. This alteration results from a T to G substitution at nucleotide position 1815, causing the asparagine (N) at amino acid position 605 to be replaced by a lysine (K). 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

0.092

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

.;T;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.68

T;.;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.5

.;M;M

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.3

.;D;.

REVEL

Benign

0.20

Sift

Uncertain

0.0010

.;D;.

Sift4G

Benign

0.087

.;T;T

Polyphen

0.29

.;B;B

Vest4

0.36, 0.36

MutPred

0.42

Gain of catalytic residue at L608 (P = 0.0094);Gain of catalytic residue at L608 (P = 0.0094);Gain of catalytic residue at L608 (P = 0.0094);

MVP

0.78

MPC

0.38

ClinPred

0.82

GERP RS

1.3

Varity_R

0.42

gMVP

0.30

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over