6-31163088-G-A

Position:

• chr6-31163088-G-A

Variant summary

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

The NM_007109.3(TCF19):​c.*371G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0709 in 1,078,400 control chromosomes in the GnomAD database, including 3,017 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 (679 hom., cov: 33)
  • Exomes 𝑓: 0.068 (2338 hom.)
• Consequence: TCF19 NM_007109.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

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]

TCF19 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• 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	Protein	UniProt
TCF19	NM_007109.3	c.*371G>A		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.*371G>A		3_prime_UTR_variant	4/4	1	NM_007109.3	ENSP00000365433.3

Frequencies

GnomAD3 genomes AF: 0.0864 AC: 13141 AN: 152180 Hom.: 679 Cov.: 33

Gnomad AFR AF: 0.0550

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0425

Gnomad SAS AF: 0.0949

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0819

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.0683 AC: 63255 AN: 926102 Hom.: 2338 Cov.: 49 AF XY: 0.0683 AC XY: 29531 AN XY: 432222

Gnomad4 AFR exome AF: 0.0551

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.133

Gnomad4 EAS exome AF: 0.0464

Gnomad4 SAS exome AF: 0.0984

Gnomad4 FIN exome AF: 0.149

Gnomad4 NFE exome AF: 0.0661

Gnomad4 OTH exome AF: 0.0756

GnomAD4 genome AF: 0.0864 AC: 13153 AN: 152298 Hom.: 679 Cov.: 33 AF XY: 0.0907 AC XY: 6755 AN XY: 74462

Gnomad4 AFR AF: 0.0550

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.0426

Gnomad4 SAS AF: 0.0949

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.0819

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0876 Hom.: 446

Bravo AF: 0.0822

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	-0.89
CADD	Benign	8.1
DANN	Benign	0.60
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: rs17190776; hg19: chr6-31130865;