6-133893387-C-G

Variant summary

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

The ENST00000237316.3(TCF21):c.*241C>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 0.31 in 152,186 control chromosomes in the GnomAD database, including 8,820 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 0.31 (8812 hom., cov: 33)
  • Exomes 𝑓: 0.38 (8 hom.)
• Consequence: TCF21 ENST00000237316.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.704

Genes affected

TCF21 (HGNC:11632): (transcription factor 21) TCF21 encodes a transcription factor of the basic helix-loop-helix family. The TCF21 product is mesoderm specific, and expressed in embryonic epicardium, mesenchyme-derived tissues of lung, gut, gonad, and both mesenchymal and glomerular epithelial cells in the kidney. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF21	NM_198392.3	c.*241C>G		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF21	ENST00000237316.3	c.*241C>G		3_prime_UTR_variant	3/3	1		P1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47160 AN: 151982 Hom.: 8802 Cov.: 33

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.331

GnomAD4 exome AF: 0.375 AC: 33 AN: 88 Hom.: 8 Cov.: 0 AF XY: 0.381 AC XY: 16 AN XY: 42

Gnomad4 FIN exome AF: 0.417

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.310 AC: 47172 AN: 152098 Hom.: 8812 Cov.: 33 AF XY: 0.321 AC XY: 23836 AN XY: 74346

Gnomad4 AFR AF: 0.0890

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.335

Alfa AF: 0.229 Hom.: 621

Bravo AF: 0.296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	5.7
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12190287; hg19: chr6-134214525;