rs11210449

chr1-74320307-A-Gchr1-74320307-A-T

Variant summary

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

The NM_015978.3(TNNI3K):c.445-11143A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,000 control chromosomes in the GnomAD database, including 30,416 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 0.59 (30416 hom., cov: 32)
• Consequence: TNNI3K NM_015978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNNI3K	NM_015978.3	c.445-11143A>G		intron_variant		ENST00000326637.8
FPGT-TNNI3K	NM_001112808.3	c.748-11143A>G		intron_variant
FPGT-TNNI3K	NM_001199327.2	c.748-11143A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNNI3K	ENST00000326637.8	c.445-11143A>G		intron_variant		1	NM_015978.3	P1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90371 AN: 151882 Hom.: 30415 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.659

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

GnomAD4 genome AF: 0.595 AC: 90381 AN: 152000 Hom.: 30416 Cov.: 32 AF XY: 0.598 AC XY: 44437 AN XY: 74286

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.686

Gnomad4 ASJ AF: 0.746

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.716

Gnomad4 NFE AF: 0.733

Gnomad4 OTH AF: 0.656

Alfa AF: 0.628 Hom.: 4287

Bravo AF: 0.578

Asia WGS AF: 0.683 AC: 2378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	12
Dann	Benign	0.79

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: rs11210449; hg19: chr1-74785991;