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: AD, Unknown Classification: STRONG, LIMITED Submitted by: PanelApp Australia, 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000372557.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNNC2	ENST00000372557.1	TSL:3	c.-42-3182C>A		intron	N/A	ENSP00000361638.1	C9J7T9

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs380397;

hg19: chr20-44456655;