rs3216869

Positions:

• chr6-31162466-ACTTC-A
• chr6-31162466-ACTTC-ACTTCCTTC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_007109.3(TCF19):​c.798-6_798-3del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0364 in 1,600,416 control chromosomes in the GnomAD database, including 2,141 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.064 (498 hom., cov: 31)
  • Exomes 𝑓: 0.034 (1643 hom.)
• Consequence: TCF19 NM_007109.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62

Genes affected

TCF19 (HGNC:11629): (transcription factor 19) This gene encodes a protein that contains a PHD-type zinc finger domain and likely functions as a transcription factor. The encoded protein plays a role proliferation and apoptosis of pancreatic beta cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF19	NM_007109.3	c.798-6_798-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000376257.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF19	ENST00000376257.8	c.798-6_798-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_007109.3	P1

Frequencies

GnomAD3 genomes AF: 0.0636 AC: 9661 AN: 151858 Hom.: 496 Cov.: 31

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0343

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.0413

Gnomad FIN AF: 0.0525

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0241

Gnomad OTH AF: 0.0638

GnomAD3 exomes AF: 0.0476 AC: 11047 AN: 232124 Hom.: 547 AF XY: 0.0454 AC XY: 5755 AN XY: 126818

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.0220

Gnomad ASJ exome AF: 0.0321

Gnomad EAS exome AF: 0.176

Gnomad SAS exome AF: 0.0381

Gnomad FIN exome AF: 0.0555

Gnomad NFE exome AF: 0.0237

Gnomad OTH exome AF: 0.0416

GnomAD4 exome AF: 0.0335 AC: 48569 AN: 1448440 Hom.: 1643 AF XY: 0.0332 AC XY: 23850 AN XY: 719414

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.0245

Gnomad4 ASJ exome AF: 0.0287

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.0360

Gnomad4 FIN exome AF: 0.0577

Gnomad4 NFE exome AF: 0.0234

Gnomad4 OTH exome AF: 0.0466

GnomAD4 genome AF: 0.0636 AC: 9665 AN: 151976 Hom.: 498 Cov.: 31 AF XY: 0.0647 AC XY: 4803 AN XY: 74278

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.0343

Gnomad4 ASJ AF: 0.0268

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.0413

Gnomad4 FIN AF: 0.0525

Gnomad4 NFE AF: 0.0241

Gnomad4 OTH AF: 0.0645

Alfa AF: 0.0405 Hom.: 42

Bravo AF: 0.0671

Asia WGS AF: 0.113 AC: 390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs3216869; hg19: chr6-31130243;