Genetic Variant TCF19:c.*1591T>C (chr6-31164308-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000706778.1(TCF19):c.*1591T>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 0.879 in 1,290,672 control chromosomes in the GnomAD database, including 500,464 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 0.92 ( 64223 hom., cov: 31)

Exomes 𝑓: 0.87 ( 436241 hom. )

Consequence

TCF19
ENST00000706778.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.57

Variant links:

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 links:

POU5F1 (HGNC:9221): (POU class 5 homeobox 1) This gene encodes a transcription factor containing a POU homeodomain that plays a key role in embryonic development and stem cell pluripotency. Aberrant expression of this gene in adult tissues is associated with tumorigenesis. This gene can participate in a translocation with the Ewing's sarcoma gene on chromosome 21, which also leads to tumor formation. Alternative splicing, as well as usage of alternative AUG and non-AUG translation initiation codons, results in multiple isoforms. One of the AUG start codons is polymorphic in human populations. Related pseudogenes have been identified on chromosomes 1, 3, 8, 10, and 12. [provided by RefSeq, Oct 2013]

POU5F1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU5F1	NM_002701.6 link	c.*293A>G		downstream_gene_variant		ENST00000259915.13	NP_002692.2	Q01860-1D2IYK3
TCF19	NM_007109.3 link	c.*1591T>C		downstream_gene_variant		ENST00000376257.8	NP_009040.2	Q9Y242A0A1U9X8M7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000259915.13 link	c.*293A>G		downstream_gene_variant		1	NM_002701.6	ENSP00000259915.7		Q01860-1
TCF19	ENST00000376257.8 link	c.*1591T>C		downstream_gene_variant		1	NM_007109.3	ENSP00000365433.3		Q9Y242

Frequencies

GnomAD3 genomes

AF:

0.917

AC:

139494

AN:

152112

Hom.:

64160

Cov.:

show subpopulations

Gnomad AFR

AF:

0.976

Gnomad AMI

AF:

0.935

Gnomad AMR

AF:

0.942

Gnomad ASJ

AF:

0.977

Gnomad EAS

AF:

0.983

Gnomad SAS

AF:

0.969

Gnomad FIN

AF:

0.888

Gnomad MID

AF:

0.978

Gnomad NFE

AF:

0.867

Gnomad OTH

AF:

0.942

GnomAD4 exome

AF:

0.874

AC:

995267

AN:

1138442

Hom.:

436241

Cov.:

AF XY:

0.877

AC XY:

484173

AN XY:

551956

show subpopulations

Gnomad4 AFR exome

AF:

0.981

Gnomad4 AMR exome

AF:

0.949

Gnomad4 ASJ exome

AF:

0.977

Gnomad4 EAS exome

AF:

0.965

Gnomad4 SAS exome

AF:

0.965

Gnomad4 FIN exome

AF:

0.878

Gnomad4 NFE exome

AF:

0.858

Gnomad4 OTH exome

AF:

0.893

GnomAD4 genome

AF:

0.917

AC:

139615

AN:

152230

Hom.:

64223

Cov.:

AF XY:

0.920

AC XY:

68485

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.976

Gnomad4 AMR

AF:

0.942

Gnomad4 ASJ

AF:

0.977

Gnomad4 EAS

AF:

0.983

Gnomad4 SAS

AF:

0.969

Gnomad4 FIN

AF:

0.888

Gnomad4 NFE

AF:

0.867

Gnomad4 OTH

AF:

0.943

Alfa

AF:

0.879

Hom.:

84148

Bravo

AF:

0.925

Asia WGS

AF:

0.968

AC:

3366

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.7

DANN

Benign

0.88

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over