rs17190776

Variant names:

• chr6-31163088-G-A
• rs17190776
• NM_007109.3:c.*371G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TCF19	NM_007109.3	c.*371G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000376257.8	NP_009040.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF19	ENST00000376257.8	c.*371G>A		3_prime_UTR_variant	Exon 4 of 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

African (AFR) AF: 0.0551 AC: 1071 AN: 19422

American (AMR) AF: 0.135 AC: 801 AN: 5916

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 1153 AN: 8650

East Asian (EAS) AF: 0.0464 AC: 511 AN: 11018

South Asian (SAS) AF: 0.0984 AC: 2130 AN: 21654

European-Finnish (FIN) AF: 0.149 AC: 604 AN: 4060

Middle Eastern (MID) AF: 0.120 AC: 253 AN: 2104

European-Non Finnish (NFE) AF: 0.0661 AC: 54240 AN: 820308

Other (OTH) AF: 0.0756 AC: 2492 AN: 32970

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

African (AFR) AF: 0.0550 AC: 2287 AN: 41568

American (AMR) AF: 0.118 AC: 1803 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 458 AN: 3472

East Asian (EAS) AF: 0.0426 AC: 221 AN: 5184

South Asian (SAS) AF: 0.0949 AC: 458 AN: 4824

European-Finnish (FIN) AF: 0.180 AC: 1908 AN: 10602

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.0819 AC: 5572 AN: 68028

Other (OTH) AF: 0.113 AC: 240 AN: 2116

Alfa AF: 0.0871 Hom.: 659

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
PhyloP100		0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17190776; hg19: chr6-31130865;