20-45823262-T-C

Variant names:

• chr20-45823262-T-C
• rs8860
• NM_003279.3:c.*86A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10

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]

ACMG classification

Verdict is Benign. Variant got -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	c.*86A>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000372555.8	NP_003270.1
TNNC2	XM_011529031.3	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	c.*86A>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_003279.3	ENSP00000361636.3
TNNC2	ENST00000372557	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.: 31

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.: 14 AF XY: 0.632 AC XY: 360422 AN XY: 569892

Gnomad4 AFR exome AF: 0.682

Gnomad4 AMR exome AF: 0.660

Gnomad4 ASJ exome AF: 0.546

Gnomad4 EAS exome AF: 0.666

Gnomad4 SAS exome AF: 0.554

Gnomad4 FIN exome AF: 0.640

Gnomad4 NFE exome AF: 0.641

Gnomad4 OTH exome AF: 0.620

GnomAD4 genome AF: 0.641 AC: 97337 AN: 151874 Hom.: 31275 Cov.: 31 AF XY: 0.637 AC XY: 47279 AN XY: 74234

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.612

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.634

Gnomad4 OTH AF: 0.633

Alfa AF: 0.634 Hom.: 38069

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	12
DANN	Benign	0.57

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

LitVar

Other links and lift over

dbSNP: rs8860; hg19: chr20-44451901; COSMIC: COSV65333233;