6-31162725-T-C

Position:

• chr6-31162725-T-C

Variant summary

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

The ENST00000376257.8(TCF19):​c.*8T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 1,608,936 control chromosomes in the GnomAD database, including 455,942 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 0.78 (46515 hom., cov: 31)
  • Exomes 𝑓: 0.75 (409427 hom.)
• Consequence: TCF19 ENST00000376257.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF19	NM_007109.3	c.*8T>C		3_prime_UTR_variant	4/4	ENST00000376257.8	NP_009040.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF19	ENST00000376257.8	c.*8T>C		3_prime_UTR_variant	4/4	1	NM_007109.3	ENSP00000365433	P1

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118525 AN: 151914 Hom.: 46476 Cov.: 31

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.817

GnomAD3 exomes AF: 0.752 AC: 181083 AN: 240728 Hom.: 68544 AF XY: 0.752 AC XY: 99218 AN XY: 131996

Gnomad AFR exome AF: 0.846

Gnomad AMR exome AF: 0.761

Gnomad ASJ exome AF: 0.859

Gnomad EAS exome AF: 0.699

Gnomad SAS exome AF: 0.703

Gnomad FIN exome AF: 0.742

Gnomad NFE exome AF: 0.750

Gnomad OTH exome AF: 0.772

GnomAD4 exome AF: 0.748 AC: 1090442 AN: 1456904 Hom.: 409427 Cov.: 92 AF XY: 0.747 AC XY: 541862 AN XY: 724940

Gnomad4 AFR exome AF: 0.851

Gnomad4 AMR exome AF: 0.770

Gnomad4 ASJ exome AF: 0.858

Gnomad4 EAS exome AF: 0.647

Gnomad4 SAS exome AF: 0.712

Gnomad4 FIN exome AF: 0.741

Gnomad4 NFE exome AF: 0.747

Gnomad4 OTH exome AF: 0.764

GnomAD4 genome AF: 0.780 AC: 118618 AN: 152032 Hom.: 46515 Cov.: 31 AF XY: 0.779 AC XY: 57886 AN XY: 74312

Gnomad4 AFR AF: 0.847

Gnomad4 AMR AF: 0.804

Gnomad4 ASJ AF: 0.862

Gnomad4 EAS AF: 0.678

Gnomad4 SAS AF: 0.687

Gnomad4 FIN AF: 0.749

Gnomad4 NFE AF: 0.747

Gnomad4 OTH AF: 0.816

Alfa AF: 0.762 Hom.: 68619

Bravo AF: 0.790

Asia WGS AF: 0.755 AC: 2626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.43
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: rs1065461; hg19: chr6-31130502; COSMIC: COSV52564592; COSMIC: COSV52564592;