3-171277546-C-T

Variant summary

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

The NM_015028.4(TNIK):c.124-49325G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0851 in 151,814 control chromosomes in the GnomAD database, including 620 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 0.085 (620 hom., cov: 32)
• Consequence: TNIK NM_015028.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNIK	NM_015028.4	c.124-49325G>A		intron_variant		ENST00000436636.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNIK	ENST00000436636.7	c.124-49325G>A		intron_variant		1	NM_015028.4	A1

Frequencies

GnomAD3 genomes AF: 0.0851 AC: 12912 AN: 151698 Hom.: 619 Cov.: 32

Gnomad AFR AF: 0.0881

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.0978

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0180

Gnomad SAS AF: 0.0585

Gnomad FIN AF: 0.0379

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0904

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.0851 AC: 12923 AN: 151814 Hom.: 620 Cov.: 32 AF XY: 0.0826 AC XY: 6125 AN XY: 74166

Gnomad4 AFR AF: 0.0881

Gnomad4 AMR AF: 0.0979

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.0180

Gnomad4 SAS AF: 0.0586

Gnomad4 FIN AF: 0.0379

Gnomad4 NFE AF: 0.0904

Gnomad4 OTH AF: 0.0991

Alfa AF: 0.0927 Hom.: 908

Bravo AF: 0.0937

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.046
Dann	Benign	0.67

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: rs13065441; hg19: chr3-170995335;