chr20-45827420-T-C

Position:

• chr20-45827420-T-C

Variant summary

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

The ENST00000372557.1(TNNC2):​c.-42-2586A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 742,138 control chromosomes in the GnomAD database, including 101,652 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 0.46 (16983 hom., cov: 29)
  • Exomes 𝑓: 0.53 (84669 hom.)
• Consequence: TNNC2 ENST00000372557.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274

Genes affected

TNNC2 (HGNC:11944): (troponin C2, fast skeletal type) Troponin (Tn), a key protein complex in the regulation of striated muscle contraction, is composed of 3 subunits. The Tn-I subunit inhibits actomyosin ATPase, the Tn-T subunit binds tropomyosin and Tn-C, while the Tn-C subunit binds calcium and overcomes the inhibitory action of the troponin complex on actin filaments. The protein encoded by this gene is the Tn-C subunit. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNNC2	XM_011529031.3	c.-42-2586A>G		intron_variant			XP_011527333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNNC2	ENST00000372557.1	c.-42-2586A>G		intron_variant		3		ENSP00000361638

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69016 AN: 150694 Hom.: 16962 Cov.: 29

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.463

GnomAD4 exome AF: 0.530 AC: 313161 AN: 591328 Hom.: 84669 AF XY: 0.522 AC XY: 159642 AN XY: 305692

Gnomad4 AFR exome AF: 0.268

Gnomad4 AMR exome AF: 0.566

Gnomad4 ASJ exome AF: 0.397

Gnomad4 EAS exome AF: 0.572

Gnomad4 SAS exome AF: 0.383

Gnomad4 FIN exome AF: 0.583

Gnomad4 NFE exome AF: 0.558

Gnomad4 OTH exome AF: 0.496

GnomAD4 genome AF: 0.458 AC: 69058 AN: 150810 Hom.: 16983 Cov.: 29 AF XY: 0.458 AC XY: 33695 AN XY: 73560

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.456

Alfa AF: 0.454 Hom.: 2724

Bravo AF: 0.449

Asia WGS AF: 0.423 AC: 1472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs373018; hg19: chr20-44456059;