chr3-171421678-A-G

Position:

• chr3-171421678-A-G

Variant summary

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

The ENST00000436636.7(TNIK):​c.57+38329T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 150,234 control chromosomes in the GnomAD database, including 44,988 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 0.77 (44988 hom., cov: 27)
• Consequence: TNIK ENST00000436636.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNIK	NM_015028.4	c.57+38329T>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+38329T>C		intron_variant		1	NM_015028.4	ENSP00000399511	A1

Frequencies

GnomAD3 genomes AF: 0.773 AC: 115977 AN: 150122 Hom.: 44941 Cov.: 27

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.783

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

GnomAD4 genome AF: 0.773 AC: 116077 AN: 150234 Hom.: 44988 Cov.: 27 AF XY: 0.772 AC XY: 56479 AN XY: 73156

Gnomad4 AFR AF: 0.841

Gnomad4 AMR AF: 0.751

Gnomad4 ASJ AF: 0.767

Gnomad4 EAS AF: 0.681

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.758

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.783

Alfa AF: 0.759 Hom.: 60326

Bravo AF: 0.777

Asia WGS AF: 0.715 AC: 2487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.72

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: rs7650598; hg19: chr3-171139467;