Variant 17-28042992-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_016231.5(NLK):c.119C>G(p.Pro40Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000088 in 1,557,212 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000094 ( 0 hom. )

Consequence

NLK
NM_016231.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.84

Variant links:

Genes affected

NLK (HGNC:29858): (nemo like kinase) Enables ubiquitin protein ligase binding activity. Involved in protein stabilization and transforming growth factor beta receptor signaling pathway. Predicted to be located in cytosol and nucleoplasm. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NLK links:

NLK (HGNC:):

NLK links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLK	NM_016231.5 linkuse as main transcript	c.119C>G	p.Pro40Arg	missense_variant	1/11	ENST00000407008.8	NP_057315.3	Q9UBE8A0A024QZ12
NLK	XM_005257988.3 linkuse as main transcript	c.119C>G	p.Pro40Arg	missense_variant	1/10		XP_005258045.1
NLK	XR_001752526.3 linkuse as main transcript	n.316C>G		non_coding_transcript_exon_variant	1/9
NLK	XR_934482.2 linkuse as main transcript	n.316C>G		non_coding_transcript_exon_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NLK	ENST00000407008.8 linkuse as main transcript	c.119C>G	p.Pro40Arg	missense_variant	1/11	1	NM_016231.5	ENSP00000384625.3	Q9UBE8
NLK	ENST00000582037.2 linkuse as main transcript	c.119C>G	p.Pro40Arg	missense_variant	1/2	2		ENSP00000464656.1	J3QSE9
NLK	ENST00000583517.1 linkuse as main transcript	n.44-96C>G		intron_variant		3
NLK	ENST00000496808.1 linkuse as main transcript	n.-38C>G		upstream_gene_variant		2		ENSP00000433117.1	H0YD75

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000237

AC:

AN:

168820

Hom.:

AF XY:

0.0000339

AC XY:

AN XY:

88538

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:

0.00

Gnomad NFE exome

AF:

0.0000591

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000939

AC:

132

AN:

1405136

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

693536

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.000119

Gnomad4 OTH exome

AF:

0.0000514

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000451

Hom.:

Bravo

AF:

0.0000340

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000267

AC:

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

Oct 08, 2024

The c.119C>G (p.P40R) alteration is located in exon 1 (coding exon 1) of the NLK gene. This alteration results from a C to G substitution at nucleotide position 119, causing the proline (P) at amino acid position 40 to be replaced by an arginine (R). 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

0.25

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Benign

0.93

DEOGEN2

Benign

0.34

T;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.80

T;T

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.57

D;D

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

0.0

N;.

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.0

N;.

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

D;.

Sift4G

Uncertain

0.018

D;T

Polyphen

0.99

D;.

Vest4

0.64

MVP

0.72

MPC

2.0

ClinPred

0.52

GERP RS

5.3

Varity_R

0.50

gMVP

0.55

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