rs7627954

chr3-171262186-T-Cchr3-171262186-T-G

Variant summary

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

The NM_015028.4(TNIK):c.124-33965A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 151,826 control chromosomes in the GnomAD database, including 24,127 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 0.56 (24127 hom., cov: 30)
• Consequence: TNIK NM_015028.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.741

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNIK	NM_015028.4	c.124-33965A>G		intron_variant		ENST00000436636.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNIK	ENST00000436636.7	c.124-33965A>G		intron_variant		1	NM_015028.4	A1

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84283 AN: 151708 Hom.: 24094 Cov.: 30

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.556 AC: 84383 AN: 151826 Hom.: 24127 Cov.: 30 AF XY: 0.553 AC XY: 41043 AN XY: 74192

Gnomad4 AFR AF: 0.675

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.603

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.530

Alfa AF: 0.528 Hom.: 9754

Bravo AF: 0.552

Asia WGS AF: 0.393 AC: 1369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.1
Dann	Benign	0.49

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: rs7627954; hg19: chr3-170979975;