rs1841

Positions:

• chr6-31162983-A-G

Variant summary

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

The NM_007109.3(TCF19):​c.*266A>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 0.0712 in 1,362,556 control chromosomes in the GnomAD database, including 3,930 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 0.065 (351 hom., cov: 33)
  • Exomes 𝑓: 0.072 (3579 hom.)
• Consequence: TCF19 NM_007109.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245

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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF19	NM_007109.3	c.*266A>G		3_prime_UTR_variant	4/4	ENST00000376257.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF19	ENST00000376257.8	c.*266A>G		3_prime_UTR_variant	4/4	1	NM_007109.3	P1

Frequencies

GnomAD3 genomes AF: 0.0652 AC: 9916 AN: 152166 Hom.: 354 Cov.: 33

Gnomad AFR AF: 0.0374

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0811

Gnomad ASJ AF: 0.0541

Gnomad EAS AF: 0.0394

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0954

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0724

Gnomad OTH AF: 0.0618

GnomAD4 exome AF: 0.0720 AC: 87150 AN: 1210272 Hom.: 3579 Cov.: 59 AF XY: 0.0735 AC XY: 42681 AN XY: 581066

Gnomad4 AFR exome AF: 0.0377

Gnomad4 AMR exome AF: 0.0923

Gnomad4 ASJ exome AF: 0.0497

Gnomad4 EAS exome AF: 0.0354

Gnomad4 SAS exome AF: 0.134

Gnomad4 FIN exome AF: 0.0920

Gnomad4 NFE exome AF: 0.0706

Gnomad4 OTH exome AF: 0.0707

GnomAD4 genome AF: 0.0651 AC: 9910 AN: 152284 Hom.: 351 Cov.: 33 AF XY: 0.0666 AC XY: 4960 AN XY: 74464

Gnomad4 AFR AF: 0.0374

Gnomad4 AMR AF: 0.0806

Gnomad4 ASJ AF: 0.0541

Gnomad4 EAS AF: 0.0397

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.0954

Gnomad4 NFE AF: 0.0724

Gnomad4 OTH AF: 0.0616

Alfa AF: 0.0750 Hom.: 442

Bravo AF: 0.0632

Asia WGS AF: 0.114 AC: 396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.7
DANN	Benign	0.81
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: rs1841; hg19: chr6-31130760;