rs4629

Positions:

• chr20-45824058-C-A
• chr20-45824058-C-G
• chr20-45824058-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_003279.3(TNNC2):​c.384G>T​(p.Thr128Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 1,613,748 control chromosomes in the GnomAD database, including 222,323 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 0.45 (16722 hom., cov: 31)
  • Exomes 𝑓: 0.53 (205601 hom.)
• Consequence: TNNC2 NM_003279.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.65

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP7: Synonymous conserved (PhyloP=-4.65 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNNC2	NM_003279.3	c.384G>T	p.Thr128Thr	synonymous_variant	5/6	ENST00000372555.8	NP_003270.1
TNNC2	XM_011529031.3	c.339G>T	p.Thr113Thr	synonymous_variant	5/6		XP_011527333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNNC2	ENST00000372555.8	c.384G>T	p.Thr128Thr	synonymous_variant	5/6	1	NM_003279.3	ENSP00000361636.3
TNNC2	ENST00000372557.1	c.339G>T	p.Thr113Thr	synonymous_variant	6/7	3		ENSP00000361638.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68167 AN: 151904 Hom.: 16710 Cov.: 31

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.452

GnomAD3 exomes AF: 0.503 AC: 126328 AN: 251366 Hom.: 33039 AF XY: 0.497 AC XY: 67470 AN XY: 135876

Gnomad AFR exome AF: 0.236

Gnomad AMR exome AF: 0.590

Gnomad ASJ exome AF: 0.388

Gnomad EAS exome AF: 0.524

Gnomad SAS exome AF: 0.366

Gnomad FIN exome AF: 0.570

Gnomad NFE exome AF: 0.545

Gnomad OTH exome AF: 0.505

GnomAD4 exome AF: 0.526 AC: 768409 AN: 1461726 Hom.: 205601 Cov.: 62 AF XY: 0.521 AC XY: 378788 AN XY: 727174

Gnomad4 AFR exome AF: 0.235

Gnomad4 AMR exome AF: 0.580

Gnomad4 ASJ exome AF: 0.388

Gnomad4 EAS exome AF: 0.559

Gnomad4 SAS exome AF: 0.372

Gnomad4 FIN exome AF: 0.577

Gnomad4 NFE exome AF: 0.546

Gnomad4 OTH exome AF: 0.490

GnomAD4 genome AF: 0.449 AC: 68195 AN: 152022 Hom.: 16722 Cov.: 31 AF XY: 0.449 AC XY: 33346 AN XY: 74294

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.445

Alfa AF: 0.514 Hom.: 27302

Bravo AF: 0.439

Asia WGS AF: 0.414 AC: 1440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	0.70
DANN	Benign	0.92

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: rs4629; hg19: chr20-44452697; COSMIC: COSV65332439;