chr3-171248627-A-G

Position:

• chr3-171248627-A-G

Variant summary

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

The NM_015028.4(TNIK):​c.124-20406T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,148 control chromosomes in the GnomAD database, including 2,010 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 0.15 (2010 hom., cov: 32)
• Consequence: TNIK NM_015028.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNIK	NM_015028.4	c.124-20406T>C		intron_variant		ENST00000436636.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNIK	ENST00000436636.7	c.124-20406T>C		intron_variant		1	NM_015028.4	A1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22408 AN: 152030 Hom.: 2005 Cov.: 32

Gnomad AFR AF: 0.0721

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.147 AC: 22415 AN: 152148 Hom.: 2010 Cov.: 32 AF XY: 0.153 AC XY: 11385 AN XY: 74382

Gnomad4 AFR AF: 0.0721

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.139

Alfa AF: 0.157 Hom.: 1613

Bravo AF: 0.138

Asia WGS AF: 0.238 AC: 825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs1501605; hg19: chr3-170966416;