Genetic Variant TCF19:c.-303C>T (chr6-31159167-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007109.3(TCF19):c.-303C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 403,756 control chromosomes in the GnomAD database, including 56,317 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 0.54 ( 22928 hom., cov: 32)

Exomes 𝑓: 0.51 ( 33389 hom. )

Consequence

TCF19
NM_007109.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.566

Publications

34 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007109.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TCF19	NM_007109.3	MANE Select	c.-303C>T	5_prime_UTR	Exon 2 of 4	NP_009040.2
TCF19	NR_199382.1		n.405C>T	non_coding_transcript_exon	Exon 2 of 5
TCF19	NM_001077511.2		c.-303C>T	5_prime_UTR	Exon 2 of 4	NP_001070979.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TCF19	ENST00000376257.8	TSL:1 MANE Select	c.-303C>T	5_prime_UTR	Exon 2 of 4	ENSP00000365433.3
TCF19	ENST00000376255.4	TSL:1	c.-303C>T	5_prime_UTR	Exon 2 of 4	ENSP00000365431.4
TCF19	ENST00000706784.1		n.456C>T	non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.545

AC:

82785

AN:

151908

Hom.:

22924

Cov.:

show subpopulations

Gnomad AFR

AF:

0.632

Gnomad AMI

AF:

0.500

Gnomad AMR

AF:

0.546

Gnomad ASJ

AF:

0.635

Gnomad EAS

AF:

0.561

Gnomad SAS

AF:

0.502

Gnomad FIN

AF:

0.453

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.504

Gnomad OTH

AF:

0.534

GnomAD4 exome

AF:

0.508

AC:

127959

AN:

251730

Hom.:

33389

Cov.:

AF XY:

0.507

AC XY:

65476

AN XY:

129122

show subpopulations

African (AFR)

AF:

0.631

AC:

4724

AN:

7482

American (AMR)

AF:

0.518

AC:

4663

AN:

8994

Ashkenazi Jewish (ASJ)

AF:

0.616

AC:

5668

AN:

9196

East Asian (EAS)

AF:

0.552

AC:

11032

AN:

19996

South Asian (SAS)

AF:

0.494

AC:

6247

AN:

12636

European-Finnish (FIN)

AF:

0.451

AC:

8007

AN:

17746

Middle Eastern (MID)

AF:

0.524

AC:

670

AN:

1278

European-Non Finnish (NFE)

AF:

0.495

AC:

78303

AN:

158126

Other (OTH)

AF:

0.531

AC:

8645

AN:

16276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

2879

5758

8637

11516

14395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

434

868

1302

1736

2170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.545

AC:

82819

AN:

152026

Hom.:

22928

Cov.:

AF XY:

0.542

AC XY:

40235

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.632

AC:

26195

AN:

41450

American (AMR)

AF:

0.545

AC:

8330

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.635

AC:

2203

AN:

3472

East Asian (EAS)

AF:

0.561

AC:

2893

AN:

5154

South Asian (SAS)

AF:

0.500

AC:

2408

AN:

4818

European-Finnish (FIN)

AF:

0.453

AC:

4783

AN:

10552

Middle Eastern (MID)

AF:

0.575

AC:

169

AN:

294

European-Non Finnish (NFE)

AF:

0.504

AC:

34256

AN:

67990

Other (OTH)

AF:

0.535

AC:

1127

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1873

3746

5620

7493

9366

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

718

1436

2154

2872

3590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.523

Hom.:

58327

Bravo

AF:

0.557

Asia WGS

AF:

0.564

AC:

1957

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.1

(source)

DANN

Benign

0.82

PhyloP100

-0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over