rs4629

Variant names:

• chr20-45824058-C-A
• rs4629
• NM_003279.3:c.384G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 36 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003279.3. 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
	TNNC2	NM_003279.3	MANE Select	c.384G>T	p.Thr128Thr	synonymous	Exon 5 of 6	NP_003270.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNNC2	ENST00000372555.8	TSL:1 MANE Select	c.384G>T	p.Thr128Thr	synonymous	Exon 5 of 6	ENSP00000361636.3
	TNNC2	ENST00000372557.1	TSL:3	c.339G>T	p.Thr113Thr	synonymous	Exon 6 of 7	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

GnomAD2 exomes AF: 0.503 AC: 126328 AN: 251366 AF XY: 0.497

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 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

African (AFR) AF: 0.235 AC: 7867 AN: 33480

American (AMR) AF: 0.580 AC: 25914 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 10150 AN: 26132

East Asian (EAS) AF: 0.559 AC: 22183 AN: 39696

South Asian (SAS) AF: 0.372 AC: 32046 AN: 86254

European-Finnish (FIN) AF: 0.577 AC: 30778 AN: 53374

Middle Eastern (MID) AF: 0.428 AC: 2467 AN: 5768

European-Non Finnish (NFE) AF: 0.546 AC: 607442 AN: 1111916

Other (OTH) AF: 0.490 AC: 29562 AN: 60392

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

African (AFR) AF: 0.244 AC: 10128 AN: 41488

American (AMR) AF: 0.499 AC: 7630 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1369 AN: 3470

East Asian (EAS) AF: 0.528 AC: 2725 AN: 5158

South Asian (SAS) AF: 0.368 AC: 1775 AN: 4820

European-Finnish (FIN) AF: 0.576 AC: 6080 AN: 10556

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.543 AC: 36897 AN: 67932

Other (OTH) AF: 0.445 AC: 940 AN: 2110

Alfa AF: 0.510 Hom.: 36578

Bravo AF: 0.439

Asia WGS AF: 0.414 AC: 1440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	0.70
DANN	Benign	0.92
PhyloP100		-4.7
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: rs4629; hg19: chr20-44452697; COSMIC: COSV65332439;