Genetic Variant TNNC2:c.*86A>G (chr20-45823262-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003279.3(TNNC2):c.*86A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 1,306,528 control chromosomes in the GnomAD database, including 265,001 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 0.64 ( 31275 hom., cov: 31)

Exomes 𝑓: 0.64 ( 233726 hom. )

Consequence

TNNC2
NM_003279.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.10

Publications

19 publications found

Variant links:

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

TNNC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNNC2	NM_003279.3 link	c.*86A>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000372555.8	NP_003270.1
TNNC2	XM_011529031.3 link	c.*86A>G		3_prime_UTR_variant	Exon 6 of 6		XP_011527333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNNC2	ENST00000372555.8 link	c.*86A>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_003279.3	ENSP00000361636.3
TNNC2	ENST00000372557.1 link	c.*86A>G		3_prime_UTR_variant	Exon 7 of 7	3		ENSP00000361638.1

Frequencies

GnomAD3 genomes

AF:

0.641

AC:

97244

AN:

151756

Hom.:

31240

Cov.:

show subpopulations

Gnomad AFR

AF:

0.681

Gnomad AMI

AF:

0.653

Gnomad AMR

AF:

0.621

Gnomad ASJ

AF:

0.556

Gnomad EAS

AF:

0.612

Gnomad SAS

AF:

0.542

Gnomad FIN

AF:

0.641

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.634

Gnomad OTH

AF:

0.637

GnomAD4 exome

AF:

0.635

AC:

733663

AN:

1154654

Hom.:

233726

Cov.:

AF XY:

0.632

AC XY:

360422

AN XY:

569892

show subpopulations

African (AFR)

AF:

0.682

AC:

16790

AN:

24634

American (AMR)

AF:

0.660

AC:

14219

AN:

21536

Ashkenazi Jewish (ASJ)

AF:

0.546

AC:

10717

AN:

19622

East Asian (EAS)

AF:

0.666

AC:

20703

AN:

31068

South Asian (SAS)

AF:

0.554

AC:

34986

AN:

63122

European-Finnish (FIN)

AF:

0.640

AC:

29201

AN:

45660

Middle Eastern (MID)

AF:

0.607

AC:

2933

AN:

4832

European-Non Finnish (NFE)

AF:

0.641

AC:

573976

AN:

895578

Other (OTH)

AF:

0.620

AC:

30138

AN:

48602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

12370

24739

37109

49478

61848

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15244

30488

45732

60976

76220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.641

AC:

97337

AN:

151874

Hom.:

31275

Cov.:

AF XY:

0.637

AC XY:

47279

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.682

AC:

28241

AN:

41438

American (AMR)

AF:

0.621

AC:

9484

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.556

AC:

1928

AN:

3466

East Asian (EAS)

AF:

0.612

AC:

3141

AN:

5132

South Asian (SAS)

AF:

0.543

AC:

2612

AN:

4808

European-Finnish (FIN)

AF:

0.641

AC:

6765

AN:

10548

Middle Eastern (MID)

AF:

0.612

AC:

180

AN:

294

European-Non Finnish (NFE)

AF:

0.634

AC:

43055

AN:

67900

Other (OTH)

AF:

0.633

AC:

1337

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

1848

3697

5545

7394

9242

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

796

1592

2388

3184

3980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.638

Hom.:

99872

Bravo

AF:

0.645

Asia WGS

AF:

0.603

AC:

2099

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

(source)

DANN

Benign

0.57

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over