rs2088885

Positions:

• chr3-171253502-C-A
• chr3-171253502-C-T

Variant summary

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

The ENST00000436636.7(TNIK):​c.124-25281G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 150,380 control chromosomes in the GnomAD database, including 23,716 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 0.55 (23716 hom., cov: 26)
• Consequence: TNIK ENST00000436636.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNIK	NM_015028.4	c.124-25281G>T		intron_variant		ENST00000436636.7	NP_055843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNIK	ENST00000436636.7	c.124-25281G>T		intron_variant		1	NM_015028.4	ENSP00000399511	A1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83163 AN: 150264 Hom.: 23687 Cov.: 26

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.526

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.554 AC: 83259 AN: 150380 Hom.: 23716 Cov.: 26 AF XY: 0.550 AC XY: 40330 AN XY: 73274

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.525

Alfa AF: 0.533 Hom.: 11253

Bravo AF: 0.551

Asia WGS AF: 0.393 AC: 1366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2088885; hg19: chr3-170971291;