rs12564445

Positions:

• chr1-201376359-G-A

Variant summary

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

The NM_001276345.2(TNNT2):​c.-15+1264C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,064 control chromosomes in the GnomAD database, including 5,980 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 0.26 (5980 hom., cov: 32)
• Consequence: TNNT2 NM_001276345.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237

Genes affected

TNNT2 (HGNC:11949): (troponin T2, cardiac type) This gene encodes the cardiac isoform of troponin T. The encoded protein is the tropomyosin-binding subunit of the troponin complex, which is located on the thin filament of striated muscles and regulates muscle contraction in response to alterations in intracellular calcium ion concentration. Mutations in this gene have been associated with familial hypertrophic cardiomyopathy as well as with dilated cardiomyopathy. [provided by RefSeq, May 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNNT2	NM_001276345.2	c.-15+1264C>T		intron_variant		ENST00000656932.1	NP_001263274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNNT2	ENST00000656932.1	c.-15+1264C>T		intron_variant			NM_001276345.2	ENSP00000499593	A2

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40089 AN: 151946 Hom.: 5962 Cov.: 32

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.264 AC: 40148 AN: 152064 Hom.: 5980 Cov.: 32 AF XY: 0.265 AC XY: 19705 AN XY: 74326

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.250

Alfa AF: 0.210 Hom.: 5718

Bravo AF: 0.267

Asia WGS AF: 0.341 AC: 1185 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12564445; hg19: chr1-201345487;