Genetic Variant NM_016231.5:c.208_210delTCGinsACT (chr17-28043081-TCG-ACT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Moderate

The NM_016231.5(NLK):c.208_210delTCGinsACT (p.Ser70Thr) variant causes a missense change. The gene NLK is a tumor suppressor gene (CancerMine: 9 TSG, 6 oncogene citations). The gene NLK is a known oncogene (CancerMine: 9 TSG, 6 oncogene citations). Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.S70T: Uncertain_significance (ClinVar VariationId 2340455, 1 star)

Frequency

Genomes: not found (cov: 32)

Consequence

NLK
NM_016231.5 missense

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.29

Publications

0 publications found

Variant links:

Genes affected

NLK (HGNC:29858): (nemo like kinase) Enables DNA-binding transcription factor binding activity; protein serine/threonine kinase activity; and ubiquitin protein ligase binding activity. Involved in several processes, including negative regulation of TORC1 signaling; 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, Jul 2025]

NLK links:

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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 ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Show applied only (1)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])

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.208_210delTCGinsACT p.Ser70Thr	missense	N/A	Prot: NP_057315.3

NLK NM_016231.5

MANE Select

HGVSc / HGVSpc.208_210delTCGinsACTp.Ser70Thr

Exon rankN/A

missense

Prot: NP_057315.3

Ensembl Transcripts

Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
NLK ENST00000407008.8	TSL:1MANE Select	c.208_210delTCGinsACT p.Ser70Thr	missense	N/A	Prot: ENSP00000384625.3 UniProt: Q9UBE8
NLK ENST00000955373.1		c.208_210delTCGinsACT p.Ser70Thr	missense	N/A	Prot: ENSP00000625432.1 UniProt: Q9UBE8
NLK ENST00000923558.1		c.208_210delTCGinsACT p.Ser70Thr	missense	N/A	Prot: ENSP00000593617.1 UniProt: A0ACI8T789

NLK ENST00000407008.8

TSL:1MANE Select

HGVSc / HGVSpc.208_210delTCGinsACTp.Ser70Thr

Exon rankN/A

missense

Prot: ENSP00000384625.3UniProt: Q9UBE8

NLK ENST00000955373.1

HGVSc / HGVSpc.208_210delTCGinsACTp.Ser70Thr

Exon rankN/A

missense

Prot: ENSP00000625432.1UniProt: Q9UBE8

NLK ENST00000923558.1

HGVSc / HGVSpc.208_210delTCGinsACTp.Ser70Thr

Exon rankN/A

missense

Prot: ENSP00000593617.1UniProt: 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 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 2 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Uncertain	5.3

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

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.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACGS-UK Somatic Oncogenicity v2025

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

MaveDB functional evidence ?

Publications

Other links and lift over

MaveDB functional evidence