rs3094187

chr6-31159167-C-T

Variant summary

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

The NM_007109.3(TCF19):c.-303C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 403,756 control chromosomes in the GnomAD database, including 56,317 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 0.54 (22928 hom., cov: 32)
  • Exomes 𝑓: 0.51 (33389 hom.)
• Consequence: TCF19 NM_007109.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.566

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF19	NM_007109.3	c.-303C>T		5_prime_UTR_variant	2/4	ENST00000376257.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF19	ENST00000376257.8	c.-303C>T		5_prime_UTR_variant	2/4	1	NM_007109.3	P1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82785 AN: 151908 Hom.: 22924 Cov.: 32

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.534

GnomAD4 exome AF: 0.508 AC: 127959 AN: 251730 Hom.: 33389 Cov.: 0 AF XY: 0.507 AC XY: 65476 AN XY: 129122

Gnomad4 AFR exome AF: 0.631

Gnomad4 AMR exome AF: 0.518

Gnomad4 ASJ exome AF: 0.616

Gnomad4 EAS exome AF: 0.552

Gnomad4 SAS exome AF: 0.494

Gnomad4 FIN exome AF: 0.451

Gnomad4 NFE exome AF: 0.495

Gnomad4 OTH exome AF: 0.531

GnomAD4 genome AF: 0.545 AC: 82819 AN: 152026 Hom.: 22928 Cov.: 32 AF XY: 0.542 AC XY: 40235 AN XY: 74286

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.535

Alfa AF: 0.516 Hom.: 19223

Bravo AF: 0.557

Asia WGS AF: 0.564 AC: 1957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.1
Dann	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3094187; hg19: chr6-31126944; COSMIC: COSV66161127; COSMIC: COSV66161127;