chr20-45826339-T-C

Variant names:

• chr20-45826339-T-C
• rs437122
• NM_003279.3:c.3+907A>G

Variant summary

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

The NM_003279.3(TNNC2):​c.3+907A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 152,122 control chromosomes in the GnomAD database, including 34,307 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 (34307 hom., cov: 32)
• Consequence: TNNC2 NM_003279.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNNC2	NM_003279.3	c.3+907A>G		intron_variant	Intron 1 of 5	ENST00000372555.8	NP_003270.1
TNNC2	XM_011529031.3	c.-42-1505A>G		intron_variant	Intron 1 of 5		XP_011527333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNNC2	ENST00000372555.8	c.3+907A>G		intron_variant	Intron 1 of 5	1	NM_003279.3	ENSP00000361636.3
TNNC2	ENST00000372557.1	c.-42-1505A>G		intron_variant	Intron 2 of 6	3		ENSP00000361638.1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101899 AN: 152004 Hom.: 34264 Cov.: 32

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.633

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: 0.671 AC: 102001 AN: 152122 Hom.: 34307 Cov.: 32 AF XY: 0.668 AC XY: 49687 AN XY: 74372

African (AFR) AF: 0.690 AC: 28641 AN: 41496

American (AMR) AF: 0.742 AC: 11348 AN: 15288

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

East Asian (EAS) AF: 0.630 AC: 3248 AN: 5152

South Asian (SAS) AF: 0.565 AC: 2724 AN: 4822

European-Finnish (FIN) AF: 0.656 AC: 6945 AN: 10588

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.660 AC: 44898 AN: 67988

Other (OTH) AF: 0.666 AC: 1406 AN: 2110

Alfa AF: 0.663 Hom.: 4887

Bravo AF: 0.681

Asia WGS AF: 0.655 AC: 2282 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	1.9
DANN	Benign	0.50
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs437122; hg19: chr20-44454978;