rs481387

chr1-74244766-C-T

Variant summary

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

The NM_015978.3(TNNI3K):c.150-4693C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 150,648 control chromosomes in the GnomAD database, including 30,169 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 0.62 (30169 hom., cov: 27)
• Consequence: TNNI3K NM_015978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.703

Genes affected

TNNI3K (HGNC:19661): (TNNI3 interacting kinase) This gene encodes a protein that belongs to the MAP kinase kinase kinase (MAPKKK) family of protein kinases. The protein contains ankyrin repeat, protein kinase and serine-rich domains and is thought to play a role in cardiac physiology. [provided by RefSeq, Sep 2012]

FPGT-TNNI3K (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNNI3K	NM_015978.3	c.150-4693C>T		intron_variant		ENST00000326637.8
FPGT-TNNI3K	NM_001112808.3	c.453-4693C>T		intron_variant
FPGT-TNNI3K	NM_001199327.2	c.453-4693C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNNI3K	ENST00000326637.8	c.150-4693C>T		intron_variant		1	NM_015978.3	P1

Frequencies

GnomAD3 genomes AF: 0.620 AC: 93379 AN: 150530 Hom.: 30115 Cov.: 27

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.621 AC: 93499 AN: 150648 Hom.: 30169 Cov.: 27 AF XY: 0.613 AC XY: 45069 AN XY: 73472

Gnomad4 AFR AF: 0.799

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.619

Alfa AF: 0.579 Hom.: 43151

Bravo AF: 0.631

Asia WGS AF: 0.471 AC: 1636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.51
Dann	Benign	0.78

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: rs481387; hg19: chr1-74710450;