20-45828016-G-T

Variant names:

• chr20-45828016-G-T
• rs380397
• ENST00000372557.1:c.-42-3182C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000372557.1(TNNC2):​c.-42-3182C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 151,958 control chromosomes in the GnomAD database, including 34,464 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 0.67 (34464 hom., cov: 31)
• Consequence: TNNC2 ENST00000372557.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103
• Publications: 10 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=-0.61).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNNC2	XM_011529031.3	c.-42-3182C>A		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.-42-3182C>A		intron_variant	Intron 2 of 6	3		ENSP00000361638.1

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102052 AN: 151840 Hom.: 34420 Cov.: 31

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.672 AC: 102154 AN: 151958 Hom.: 34464 Cov.: 31 AF XY: 0.670 AC XY: 49734 AN XY: 74264

African (AFR) AF: 0.697 AC: 28878 AN: 41428

American (AMR) AF: 0.743 AC: 11344 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1983 AN: 3472

East Asian (EAS) AF: 0.630 AC: 3258 AN: 5174

South Asian (SAS) AF: 0.565 AC: 2717 AN: 4808

European-Finnish (FIN) AF: 0.657 AC: 6927 AN: 10550

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.660 AC: 44830 AN: 67948

Other (OTH) AF: 0.666 AC: 1408 AN: 2114

Alfa AF: 0.668 Hom.: 48796

Bravo AF: 0.683

Asia WGS AF: 0.656 AC: 2286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.3
DANN	Benign	0.65
PhyloP100		0.10
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs380397; hg19: chr20-44456655;