rs1247813

Variant names:

• chr1-74450244-G-A
• rs274594
• NM_015978.3:c.2011+10622G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_015978.3(TNNI3K):​c.2011+10622G>A variant causes a intron change. The variant allele was found at a frequency of 0.00723 in 151,400 control chromosomes in the GnomAD database, including 9 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 0.0072 (9 hom., cov: 26)
• Consequence: TNNI3K NM_015978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: No conservation score assigned
• Publications: 0 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=-0.98).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00723 (1095/151400) while in subpopulation AFR AF = 0.0247 (1016/41216). AF 95% confidence interval is 0.0234. There are 9 homozygotes in GnomAd4. There are 518 alleles in the male GnomAd4 subpopulation. Median coverage is 26. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1095 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNNI3K	NM_015978.3	MANE Select	c.2011+10622G>A		intron	N/A	NP_057062.1	Q59H18-2
	FPGT-TNNI3K	NM_001112808.3		c.2314+10622G>A		intron	N/A	NP_001106279.3
	FPGT-TNNI3K	NM_001199327.2		c.2314+10622G>A		intron	N/A	NP_001186256.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNNI3K	ENST00000326637.8	TSL:1 MANE Select	c.2011+10622G>A		intron	N/A	ENSP00000322251.3	Q59H18-2
	FPGT-TNNI3K	ENST00000557284.7	TSL:2	c.2314+10622G>A		intron	N/A	ENSP00000450895.3
	FPGT-TNNI3K	ENST00000370899.7	TSL:2	c.2314+10622G>A		intron	N/A	ENSP00000359936.3

Frequencies

GnomAD3 genomes AF: 0.00722 AC: 1093 AN: 151284 Hom.: 9 Cov.: 26

Gnomad AFR AF: 0.0247

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00324

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00578

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

GnomAD4 genome AF: 0.00723 AC: 1095 AN: 151400 Hom.: 9 Cov.: 26 AF XY: 0.00701 AC XY: 518 AN XY: 73942

African (AFR) AF: 0.0247 AC: 1016 AN: 41216

American (AMR) AF: 0.00323 AC: 49 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.000210 AC: 1 AN: 4768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000251 AC: 17 AN: 67860

Other (OTH) AF: 0.00572 AC: 12 AN: 2098

Alfa AF: 0.00695 Hom.: 2

Bravo AF: 0.00885

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.6
DANN	Benign	0.84
Mutation Taster		=100/0	polymorphism

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: rs274594; hg19: chr1-74915928;