17-28192178-C-T

Variant names:

• chr17-28192178-C-T
• rs3182380
• NM_016231.5:c.1494C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_016231.5(NLK):​c.1494C>T​(p.Ile498Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.048 in 1,605,330 control chromosomes in the GnomAD database, including 2,229 homozygotes. 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: 𝑓 0.038 (170 hom., cov: 32)
  • Exomes 𝑓: 0.049 (2059 hom.)
• Consequence: NLK NM_016231.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96
• Publications: 9 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]

ENSG00000301334 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP7: Synonymous conserved (PhyloP=2.96 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0535 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLK	NM_016231.5	MANE Select	c.1494C>T	p.Ile498Ile	synonymous	Exon 10 of 11	NP_057315.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLK	ENST00000407008.8	TSL:1 MANE Select	c.1494C>T	p.Ile498Ile	synonymous	Exon 10 of 11	ENSP00000384625.3
	NLK	ENST00000584878.1	TSL:1	n.338C>T		non_coding_transcript_exon	Exon 2 of 3
	NLK	ENST00000496808.1	TSL:2	n.1338C>T		non_coding_transcript_exon	Exon 10 of 12	ENSP00000433117.1

Frequencies

GnomAD3 genomes AF: 0.0385 AC: 5855 AN: 152176 Hom.: 169 Cov.: 32

Gnomad AFR AF: 0.00992

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.0388

Gnomad ASJ AF: 0.0997

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0176

Gnomad FIN AF: 0.0397

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0550

Gnomad OTH AF: 0.0459

GnomAD2 exomes AF: 0.0403 AC: 9916 AN: 245784 AF XY: 0.0417

Gnomad AFR exome AF: 0.00913

Gnomad AMR exome AF: 0.0308

Gnomad ASJ exome AF: 0.0940

Gnomad EAS exome AF: 0.0000550

Gnomad FIN exome AF: 0.0426

Gnomad NFE exome AF: 0.0543

Gnomad OTH exome AF: 0.0570

GnomAD4 exome AF: 0.0490 AC: 71246 AN: 1453036 Hom.: 2059 Cov.: 27 AF XY: 0.0483 AC XY: 34896 AN XY: 722856

African (AFR) AF: 0.00767 AC: 256 AN: 33390

American (AMR) AF: 0.0328 AC: 1455 AN: 44338

Ashkenazi Jewish (ASJ) AF: 0.0940 AC: 2437 AN: 25918

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39654

South Asian (SAS) AF: 0.0181 AC: 1547 AN: 85402

European-Finnish (FIN) AF: 0.0431 AC: 2294 AN: 53254

Middle Eastern (MID) AF: 0.0539 AC: 309 AN: 5738

European-Non Finnish (NFE) AF: 0.0542 AC: 59854 AN: 1105286

Other (OTH) AF: 0.0514 AC: 3089 AN: 60056

GnomAD4 genome AF: 0.0384 AC: 5855 AN: 152294 Hom.: 170 Cov.: 32 AF XY: 0.0373 AC XY: 2774 AN XY: 74450

African (AFR) AF: 0.00987 AC: 410 AN: 41558

American (AMR) AF: 0.0387 AC: 593 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0997 AC: 346 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0176 AC: 85 AN: 4824

European-Finnish (FIN) AF: 0.0397 AC: 421 AN: 10604

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0550 AC: 3741 AN: 68026

Other (OTH) AF: 0.0454 AC: 96 AN: 2114

Alfa AF: 0.0509 Hom.: 740

Bravo AF: 0.0397

Asia WGS AF: 0.00982 AC: 35 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	13
DANN	Benign	0.72
PhyloP100		3.0
Mutation Taster		=94/6	polymorphism (auto)

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: rs3182380; hg19: chr17-26519204;