chr20-45828710-T-C

Position:

• chr20-45828710-T-C

Variant summary

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

The ENST00000372557.1(TNNC2):​c.-42-3876A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,250 control chromosomes in the GnomAD database, including 15,579 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 0.42 (15579 hom., cov: 30)
• Consequence: TNNC2 ENST00000372557.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254

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=-0.84).
• 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.-42-3876A>G		intron_variant			XP_011527333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNNC2	ENST00000372557.1	c.-42-3876A>G		intron_variant		3		ENSP00000361638.1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64197 AN: 151130 Hom.: 15564 Cov.: 30

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.425 AC: 64223 AN: 151250 Hom.: 15579 Cov.: 30 AF XY: 0.425 AC XY: 31392 AN XY: 73840

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.433

Alfa AF: 0.468 Hom.: 2205

Bravo AF: 0.409

Asia WGS AF: 0.350 AC: 1218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs383112; hg19: chr20-44457349;