rs17190811

Positions:

• chr6-31164060-A-T

Variant summary

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

The NM_007109.3(TCF19):​c.*1343A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0698 in 1,009,916 control chromosomes in the GnomAD database, including 2,703 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 0.086 (676 hom., cov: 32)
  • Exomes 𝑓: 0.067 (2027 hom.)
• Consequence: TCF19 NM_007109.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309

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 (AMR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF19	NM_007109.3	c.*1343A>T		3_prime_UTR_variant	4/4	ENST00000376257.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF19	ENST00000376257.8	c.*1343A>T		3_prime_UTR_variant	4/4	1	NM_007109.3	P1

Frequencies

GnomAD3 genomes AF: 0.0863 AC: 13127 AN: 152150 Hom.: 676 Cov.: 32

Gnomad AFR AF: 0.0550

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0429

Gnomad SAS AF: 0.0945

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0819

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.0669 AC: 57337 AN: 857648 Hom.: 2027 Cov.: 32 AF XY: 0.0667 AC XY: 26470 AN XY: 396744

Gnomad4 AFR exome AF: 0.0561

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.0470

Gnomad4 SAS exome AF: 0.0992

Gnomad4 FIN exome AF: 0.152

Gnomad4 NFE exome AF: 0.0653

Gnomad4 OTH exome AF: 0.0747

GnomAD4 genome AF: 0.0863 AC: 13139 AN: 152268 Hom.: 676 Cov.: 32 AF XY: 0.0906 AC XY: 6747 AN XY: 74442

Gnomad4 AFR AF: 0.0550

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.0430

Gnomad4 SAS AF: 0.0946

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.0819

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0833 Hom.: 75

Bravo AF: 0.0821

Asia WGS AF: 0.0780 AC: 272 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	3.7
DANN	Benign	0.56

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: rs17190811; hg19: chr6-31131837; COSMIC: COSV105012453; COSMIC: COSV105012453;