rs2292006

Positions:

• chr3-171140617-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015028.4(TNIK):​c.1222-108A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 955,710 control chromosomes in the GnomAD database, including 265,984 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 0.75 (42655 hom., cov: 31)
  • Exomes 𝑓: 0.74 (223329 hom.)
• Consequence: TNIK NM_015028.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109

Genes affected

TNIK (HGNC:30765): (TRAF2 and NCK interacting kinase) Wnt signaling plays important roles in carcinogenesis and embryonic development. The protein encoded by this gene is a serine/threonine kinase that functions as an activator of the Wnt signaling pathway. Mutations in this gene are associated with an autosomal recessive form of cognitive disability. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2017]

LOC105374216 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNIK	NM_015028.4	c.1222-108A>C		intron_variant		ENST00000436636.7	NP_055843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNIK	ENST00000436636.7	c.1222-108A>C		intron_variant		1	NM_015028.4	ENSP00000399511	A1

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113440 AN: 151856 Hom.: 42621 Cov.: 31

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.723

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.707

GnomAD4 exome AF: 0.743 AC: 597493 AN: 803736 Hom.: 223329 AF XY: 0.741 AC XY: 313918 AN XY: 423778

Gnomad4 AFR exome AF: 0.740

Gnomad4 AMR exome AF: 0.782

Gnomad4 ASJ exome AF: 0.741

Gnomad4 EAS exome AF: 0.572

Gnomad4 SAS exome AF: 0.709

Gnomad4 FIN exome AF: 0.838

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 0.738

GnomAD4 genome AF: 0.747 AC: 113529 AN: 151974 Hom.: 42655 Cov.: 31 AF XY: 0.749 AC XY: 55618 AN XY: 74256

Gnomad4 AFR AF: 0.742

Gnomad4 AMR AF: 0.752

Gnomad4 ASJ AF: 0.733

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.720

Gnomad4 FIN AF: 0.850

Gnomad4 NFE AF: 0.750

Gnomad4 OTH AF: 0.702

Alfa AF: 0.739 Hom.: 34466

Bravo AF: 0.738

Asia WGS AF: 0.639 AC: 2225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.5
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs2292006; hg19: chr3-170858406; COSMIC: COSV52677070;