20-45828710-T-C

Variant names:

• chr20-45828710-T-C
• rs383112
• ENST00000372557.1:c.-42-3876A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

TNNC2 Gene-Disease associations (from GenCC):

• congenital myopathy 15

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TNNC2	XM_011529031.3	c.-42-3876A>G		intron_variant	Intron 1 of 5		XP_011527333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNNC2	ENST00000372557.1	c.-42-3876A>G		intron_variant	Intron 2 of 6	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

African (AFR) AF: 0.176 AC: 7244 AN: 41070

American (AMR) AF: 0.482 AC: 7320 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1355 AN: 3464

East Asian (EAS) AF: 0.407 AC: 2081 AN: 5110

South Asian (SAS) AF: 0.369 AC: 1761 AN: 4766

European-Finnish (FIN) AF: 0.569 AC: 5972 AN: 10488

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36923 AN: 67852

Other (OTH) AF: 0.433 AC: 911 AN: 2104

Alfa AF: 0.456 Hom.: 2219

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
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs383112; hg19: chr20-44457349;