NM_016231.5:c.208T>A

Variant names:

Variant summary

Our verdict is The variant received 0 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Moderate

The NM_016231.5(NLK):c.208T>A (p.Ser70Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.000000704 (AC=1) in the gnomAD database across 1,420,218 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.000000917. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain Significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

NLK
NM_016231.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.29

Publications

0 publications found

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

new If you want to explore the variant's impact on the transcript NM_016231.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 points.

PM2

Very rare in gnomAD for AR/unknown gene (popmax AF < threshold/10) — PM2; GnomAD popmax AF = 0.000000917 — very rare for unknown gene (threshold 0.001) — PM2 moderate.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Moderate).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_016231.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLK	NM_016231.5	MANE Select	c.208T>A	p.Ser70Thr	missense	Exon 1 of 11	NP_057315.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NLK	ENST00000407008.8	TSL:1 MANE Select	c.208T>A	p.Ser70Thr	missense	Exon 1 of 11	ENSP00000384625.3	Q9UBE8
NLK	ENST00000955373.1		c.208T>A	p.Ser70Thr	missense	Exon 2 of 12	ENSP00000625432.1	Q9UBE8
NLK	ENST00000923558.1		c.208T>A	p.Ser70Thr	missense	Exon 1 of 11	ENSP00000593617.1	A0ACI8T789

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes					32
GnomAD4 exome	7.04e-7	1	0	1420218	31
GnomAD4 genome					32
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	0.00	0	0	13470

Showing 4 sources

Case/control cohorts

Cohort	Cases			Controls
Cohort	AF	AC	AN	AF	AC	AN
SCHEMA (Schizophrenia)	0.00	0	63156	0.00000818	1	122294

Showing 1 cohortAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational Scores

Algorithm	Calibrated prediction	Prediction	Score
AlphaGenome AVI	Pathogenic	-	21
AlphaMissense	Benign	-	0.081
BayesDel_addAF	Benign	T	-0.15
BayesDel_noAF	Benign	-	-0.45
CADD	Benign	-	23
DANN	Benign	-	0.91
DEOGEN2	Benign	T	0.30
Eigen	Benign	-	-0.10
Eigen_PC	Benign	-	0.12
FATHMM_MKL	Uncertain	D	0.95
FuncVEP CTI	Benign	-	0.0086
GPN-Star LLR	N/A	-	-8.2
GPN-Star score	N/A	-	8.2
LIST_S2	Benign	T	0.72
M_CAP	Benign	D	0.032
MetaRNN	Benign	T	0.16
MetaSVM	Benign	T	-0.77
MutationAssessor	Benign	N	0.0
PhyloP100	Uncertain	-	5.3
popEVE	Benign	-	-3.2
PrimateAI	Uncertain	T	0.65
PromoterAI	N/A	Neutral	-0.045
PROVEAN	Benign	N	0.0
REVEL	Benign	-	0.092
Sift	Benign	T	0.17
Sift4G	Benign	T	0.59
Varity_R	N/A	-	0.12
VESM-3B	Benign	-	-3.1

Showing 28 of 28 scores

Splicing Scores

Algorithm	Calibrated prediction	Prediction	Score
Pangolin (max)	Benign	-	0.010
SpliceAI score (max)	Benign	- Details are displayed if max score is > 0.2	0.0

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Case/control cohorts

ClinVar

Computational Scores

Splicing Scores

Publications

Other links and lift over