Variant 17-28042979-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_016231.5(NLK):c.106C>T(p.Pro36Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000027 in 1,557,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

NLK
NM_016231.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.19

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.034779996).

BS2

High AC in GnomAd4 at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLK	NM_016231.5 link	c.106C>T	p.Pro36Ser	missense_variant	1/11	ENST00000407008.8	NP_057315.3	Q9UBE8A0A024QZ12
NLK	XM_005257988.3 link	c.106C>T	p.Pro36Ser	missense_variant	1/10		XP_005258045.1
NLK	XR_001752526.3 link	n.303C>T		non_coding_transcript_exon_variant	1/9
NLK	XR_934482.2 link	n.303C>T		non_coding_transcript_exon_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NLK	ENST00000407008.8 link	c.106C>T	p.Pro36Ser	missense_variant	1/11	1	NM_016231.5	ENSP00000384625.3	Q9UBE8
NLK	ENST00000582037.2 link	c.106C>T	p.Pro36Ser	missense_variant	1/2	2		ENSP00000464656.1	J3QSE9
NLK	ENST00000583517.1 link	n.44-109C>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

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:

0.0000147

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.0000354

AC:

AN:

169344

Hom.:

AF XY:

0.0000225

AC XY:

AN XY:

88854

show subpopulations

Gnomad AFR exome

AF:

0.000521

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:

0.00

Gnomad OTH exome

AF:

0.000210

GnomAD4 exome

AF:

0.0000121

AC:

AN:

1405144

Hom.:

Cov.:

AF XY:

0.0000144

AC XY:

AN XY:

693536

show subpopulations

Gnomad4 AFR exome

AF:

0.000534

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:

0.00

GnomAD4 genome

AF:

0.000164

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.000530

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:

0.0000147

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.000147

ESP6500AA

AF:

0.000685

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000356

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

Feb 21, 2024

The c.106C>T (p.P36S) alteration is located in exon 1 (coding exon 1) of the NLK gene. This alteration results from a C to T substitution at nucleotide position 106, causing the proline (P) at amino acid position 36 to be replaced by a serine (S). 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

0.10

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Benign

0.77

DEOGEN2

Benign

0.27

T;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.38

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.035

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

N;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.16

N;.

REVEL

Benign

0.20

Sift

Benign

0.40

T;.

Sift4G

Benign

0.23

T;T

Polyphen

0.0

B;.

Vest4

0.21

MVP

0.45

MPC

1.7

ClinPred

0.11

GERP RS

4.4

Varity_R

0.066

gMVP

0.39

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