chr3-171440696-C-G

Position:

• chr3-171440696-C-G

Variant summary

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

The NM_015028.4(TNIK):​c.57+19311G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,118 control chromosomes in the GnomAD database, including 4,514 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 0.23 (4514 hom., cov: 32)
• Consequence: TNIK NM_015028.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.187

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 (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNIK	NM_015028.4	c.57+19311G>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.57+19311G>C		intron_variant		1	NM_015028.4	ENSP00000399511	A1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34407 AN: 152000 Hom.: 4506 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.226 AC: 34438 AN: 152118 Hom.: 4514 Cov.: 32 AF XY: 0.226 AC XY: 16795 AN XY: 74388

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.230

Alfa AF: 0.0767 Hom.: 98

Bravo AF: 0.246

Asia WGS AF: 0.356 AC: 1235 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	1.7
DANN	Benign	0.42

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: rs2422299; hg19: chr3-171158485;