dbSNP rs3130933: TCF19:c.*1591T>A (chr6-31164308-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000706778.1(TCF19):c.*1591T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TCF19
ENST00000706778.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.57

Publications

32 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000706778.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
POU5F1	NM_002701.6	MANE Select	c.*293A>T	downstream_gene	N/A	NP_002692.2
TCF19	NM_007109.3	MANE Select	c.*1591T>A	downstream_gene	N/A	NP_009040.2	A0A1U9X8M7
TCF19	NM_001077511.2		c.*1591T>A	downstream_gene	N/A	NP_001070979.1	A0A1U9X8M7

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
TCF19	ENST00000706778.1	c.*1591T>A	3_prime_UTR	Exon 5 of 5	ENSP00000516543.1	Q9Y242
TCF19	ENST00000706779.1	c.*1591T>A	3_prime_UTR	Exon 3 of 3	ENSP00000516544.1	Q9Y242
TCF19	ENST00000706780.1	c.*1591T>A	3_prime_UTR	Exon 5 of 5	ENSP00000516545.1	Q9Y242

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1139666

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

552488

African (AFR)

AF:

0.00

AC:

AN:

25282

American (AMR)

AF:

0.00

AC:

AN:

17276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16826

East Asian (EAS)

AF:

0.00

AC:

AN:

28814

South Asian (SAS)

AF:

0.00

AC:

AN:

57534

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35282

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3170

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

908566

Other (OTH)

AF:

0.00

AC:

AN:

46916

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.5

(source)

DANN

Benign

0.88

PhyloP100

-1.6

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over