13-52072067-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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. 17/22 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, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.41

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

ALG11-congenital disorder of glycosylation
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ALG11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 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 VariationId is 2643825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365552.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK5	NM_001365552.1	MANE Select	c.1726A>G	p.Met576Val	missense	Exon 20 of 24	NP_001352481.1	A0A8I5KQI9
	NEK5	NM_199289.3		c.1801A>G	p.Met601Val	missense	Exon 21 of 22	NP_954983.1	Q6P3R8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEK5	ENST00000684899.1	MANE Select	c.1726A>G	p.Met576Val	missense	Exon 20 of 24	ENSP00000509632.1	A0A8I5KQI9
NEK5	ENST00000355568.8	TSL:1	c.1801A>G	p.Met601Val	missense	Exon 21 of 22	ENSP00000347767.4	Q6P3R8
NEK5	ENST00000647945.2		c.1801A>G	p.Met601Val	missense	Exon 21 of 25	ENSP00000497892.1	A0A3B3ITQ6

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

GnomAD2 exomes

AF:

0.00259

AC:

645

AN:

248956

AF XY:

0.00271

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 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

African (AFR)

AF:

0.000690

AC:

AN:

33340

American (AMR)

AF:

0.00136

AC:

AN:

44202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26032

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39656

South Asian (SAS)

AF:

0.000163

AC:

AN:

85864

European-Finnish (FIN)

AF:

0.00371

AC:

198

AN:

53346

Middle Eastern (MID)

AF:

0.000700

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.00433

AC:

4805

AN:

1109310

Other (OTH)

AF:

0.00252

AC:

152

AN:

60236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

231

461

692

922

1153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

344

516

688

860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00251

AC:

382

AN:

152346

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

182

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.000649

AC:

AN:

41588

American (AMR)

AF:

0.00124

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00424

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00423

AC:

288

AN:

68034

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00369

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.074

(source)

DANN

Benign

0.32

DEOGEN2

Benign

0.015

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.47

M_CAP

Benign

0.0062

MetaRNN

Benign

0.0045

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.17

PhyloP100

-1.4

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.46

REVEL

Benign

0.077

Sift

Benign

1.0

Sift4G

Benign

0.75

Polyphen

0.0

Vest4

0.036

MVP

0.28

MPC

0.060

ClinPred

0.00080

GERP RS

-1.5

Varity_R

0.047

gMVP

0.038

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over