rs1247813

Positions:

• chr1-74450244-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.98).
• 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 male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1095 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNNI3K	NM_015978.3	c.2011+10622G>A		intron_variant		ENST00000326637.8	NP_057062.1
FPGT-TNNI3K	NM_001112808.3	c.2314+10622G>A		intron_variant			NP_001106279.3
FPGT-TNNI3K	NM_001199327.2	c.2314+10622G>A		intron_variant			NP_001186256.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNNI3K	ENST00000326637.8	c.2011+10622G>A		intron_variant		1	NM_015978.3	ENSP00000322251	P1
TNNI3K	ENST00000370889.2	n.558+10622G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0247

Gnomad4 AMR AF: 0.00323

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000251

Gnomad4 OTH AF: 0.00572

Alfa AF: 0.00695 Hom.: 2

Bravo AF: 0.00885

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.6
DANN	Benign	0.84

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: rs274594; hg19: chr1-74915928;