rs481387

Variant names:

• chr1-74244766-C-T
• rs481387
• NM_015978.3:c.150-4693C>T

Variant summary

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

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:42952): (FPGT-TNNI3K readthrough) Enables protein C-terminus binding activity; protein kinase activity; and troponin I binding activity. Involved in protein phosphorylation and regulation of heart contraction. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015978.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNNI3K	NM_015978.3	MANE Select	c.150-4693C>T		intron	N/A	NP_057062.1
	FPGT-TNNI3K	NM_001112808.3		c.453-4693C>T		intron	N/A	NP_001106279.3
	FPGT-TNNI3K	NM_001199327.2		c.453-4693C>T		intron	N/A	NP_001186256.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNNI3K	ENST00000326637.8	TSL:1 MANE Select	c.150-4693C>T		intron	N/A	ENSP00000322251.3
	FPGT-TNNI3K	ENST00000557284.7	TSL:2	c.453-4693C>T		intron	N/A	ENSP00000450895.3
	FPGT-TNNI3K	ENST00000370899.7	TSL:2	c.453-4693C>T		intron	N/A	ENSP00000359936.3

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

African (AFR) AF: 0.799 AC: 32752 AN: 41004

American (AMR) AF: 0.596 AC: 8960 AN: 15044

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1597 AN: 3456

East Asian (EAS) AF: 0.272 AC: 1391 AN: 5110

South Asian (SAS) AF: 0.490 AC: 2308 AN: 4708

European-Finnish (FIN) AF: 0.532 AC: 5514 AN: 10366

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39136 AN: 67680

Other (OTH) AF: 0.619 AC: 1293 AN: 2088

Alfa AF: 0.589 Hom.: 102379

Bravo AF: 0.631

Asia WGS AF: 0.471 AC: 1636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.51
DANN	Benign	0.78
PhyloP100		-0.70
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: rs481387; hg19: chr1-74710450;