17-28043059-C-T

Variant names:

• chr17-28043059-C-T
• rs1908919566
• NM_016231.5:c.186C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_016231.5(NLK):​c.186C>T​(p.His62His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,412,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NLK NM_016231.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=1 with no splicing effect.

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLK	NM_016231.5	MANE Select	c.186C>T	p.His62His	synonymous	Exon 1 of 11	NP_057315.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLK	ENST00000407008.8	TSL:1 MANE Select	c.186C>T	p.His62His	synonymous	Exon 1 of 11	ENSP00000384625.3	Q9UBE8
	NLK	ENST00000955373.1		c.186C>T	p.His62His	synonymous	Exon 2 of 12	ENSP00000625432.1
	NLK	ENST00000923558.1		c.186C>T	p.His62His	synonymous	Exon 1 of 11	ENSP00000593617.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000212 AC: 3 AN: 1412236 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 698148

African (AFR) AF: 0.00 AC: 0 AN: 32058

American (AMR) AF: 0.00 AC: 0 AN: 36248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25352

East Asian (EAS) AF: 0.00 AC: 0 AN: 36624

South Asian (SAS) AF: 0.00 AC: 0 AN: 81666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.00000276 AC: 3 AN: 1085710

Other (OTH) AF: 0.00 AC: 0 AN: 58546

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	10
DANN	Benign	0.88
PhyloP100		1.0
PromoterAI		0.071	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs1908919566; hg19: chr17-26370085;