Variant 17-28043070-A-G 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_016231.5(NLK):c.197A>G(p.Gln66Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000141 in 1,415,886 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NLK
NM_016231.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.38

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:

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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=0.1755093).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLK	NM_016231.5 link	c.197A>G	p.Gln66Arg	missense_variant	1/11	ENST00000407008.8	NP_057315.3	Q9UBE8A0A024QZ12
NLK	XM_005257988.3 link	c.197A>G	p.Gln66Arg	missense_variant	1/10		XP_005258045.1
NLK	XR_001752526.3 link	n.394A>G		non_coding_transcript_exon_variant	1/9
NLK	XR_934482.2 link	n.394A>G		non_coding_transcript_exon_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NLK	ENST00000407008.8 link	c.197A>G	p.Gln66Arg	missense_variant	1/11	1	NM_016231.5	ENSP00000384625.3	Q9UBE8
NLK	ENST00000582037.2 link	c.197A>G	p.Gln66Arg	missense_variant	1/2	2		ENSP00000464656.1	J3QSE9
NLK	ENST00000496808.1 link	n.41A>G		non_coding_transcript_exon_variant	1/12	2		ENSP00000433117.1	H0YD75
NLK	ENST00000583517.1 link	n.44-18A>G		intron_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1415886

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

700370

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:

0.00000184

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Sep 01, 2021

The c.197A>G (p.Q66R) alteration is located in exon 1 (coding exon 1) of the NLK gene. This alteration results from a A to G substitution at nucleotide position 197, causing the glutamine (Q) at amino acid position 66 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

0.18

BayesDel_addAF

Benign

0.00044

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.28

T;.

Eigen

Benign

-0.059

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.55

N;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.46

N;.

REVEL

Benign

0.14

Sift

Uncertain

0.0080

D;.

Sift4G

Benign

0.82

T;T

Polyphen

0.039

B;.

Vest4

0.29

MutPred

0.14

Gain of MoRF binding (P = 0.0532);Gain of MoRF binding (P = 0.0532);

MVP

0.71

MPC

1.1

ClinPred

0.79

GERP RS

5.4

Varity_R

0.29

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

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