chr1-74438669-C-T

Variant names:

• chr1-74438669-C-T
• rs17095322
• NM_015978.3:c.1879-821C>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.1879-821C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0674 in 151,956 control chromosomes in the GnomAD database, including 341 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 0.067 (341 hom., cov: 31)
• Consequence: TNNI3K NM_015978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0949 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNNI3K	NM_015978.3	MANE Select	c.1879-821C>T		intron	N/A	NP_057062.1	Q59H18-2
	FPGT-TNNI3K	NM_001112808.3		c.2182-821C>T		intron	N/A	NP_001106279.3
	FPGT-TNNI3K	NM_001199327.2		c.2182-821C>T		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.1879-821C>T		intron	N/A	ENSP00000322251.3	Q59H18-2
	FPGT-TNNI3K	ENST00000557284.7	TSL:2	c.2182-821C>T		intron	N/A	ENSP00000450895.3
	FPGT-TNNI3K	ENST00000370899.7	TSL:2	c.2182-821C>T		intron	N/A	ENSP00000359936.3

Frequencies

GnomAD3 genomes AF: 0.0673 AC: 10225 AN: 151838 Hom.: 339 Cov.: 31

Gnomad AFR AF: 0.0763

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0487

Gnomad ASJ AF: 0.0401

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.0713

Gnomad FIN AF: 0.0553

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0662

Gnomad OTH AF: 0.0523

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

GnomAD4 genome AF: 0.0674 AC: 10239 AN: 151956 Hom.: 341 Cov.: 31 AF XY: 0.0671 AC XY: 4985 AN XY: 74296

African (AFR) AF: 0.0764 AC: 3166 AN: 41436

American (AMR) AF: 0.0486 AC: 741 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0401 AC: 139 AN: 3466

East Asian (EAS) AF: 0.102 AC: 526 AN: 5152

South Asian (SAS) AF: 0.0714 AC: 344 AN: 4820

European-Finnish (FIN) AF: 0.0553 AC: 585 AN: 10584

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0662 AC: 4499 AN: 67930

Other (OTH) AF: 0.0517 AC: 109 AN: 2108

Alfa AF: 0.0638 Hom.: 569

Bravo AF: 0.0688

Asia WGS AF: 0.0670 AC: 235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.62
PhyloP100		-0.30
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: rs17095322; hg19: chr1-74904353;