rs7627954

Variant names:

• chr3-171262186-T-C
• rs7627954
• NM_015028.4:c.124-33965A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-171262186-T-C
• chr3-171262186-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

TNIK Gene-Disease associations (from GenCC):

• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability, autosomal recessive 54

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TNIK	NM_015028.4	c.124-33965A>G		intron_variant	Intron 2 of 32	ENST00000436636.7	NP_055843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNIK	ENST00000436636.7	c.124-33965A>G		intron_variant	Intron 2 of 32	1	NM_015028.4	ENSP00000399511.2

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

African (AFR) AF: 0.675 AC: 27921 AN: 41374

American (AMR) AF: 0.463 AC: 7068 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1747 AN: 3468

East Asian (EAS) AF: 0.340 AC: 1754 AN: 5156

South Asian (SAS) AF: 0.430 AC: 2067 AN: 4806

European-Finnish (FIN) AF: 0.603 AC: 6357 AN: 10548

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35613 AN: 67898

Other (OTH) AF: 0.530 AC: 1117 AN: 2108

Alfa AF: 0.529 Hom.: 10849

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
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7627954; hg19: chr3-170979975;