Genetic Variant TCF19:c.*1213T>A (chr6-31163930-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 NM_007109.3(TCF19):c.*1213T>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 0.0000012 in 833,576 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)

Exomes 𝑓: 0.0000012 ( 0 hom. )

Consequence

TCF19
NM_007109.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.211

Publications

0 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: 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=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF19	NM_007109.3 link	c.*1213T>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000376257.8	NP_009040.2	Q9Y242A0A1U9X8M7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF19	ENST00000376257.8 link	c.*1213T>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_007109.3	ENSP00000365433.3		Q9Y242

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000120

AC:

AN:

833576

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

384960

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

15788

American (AMR)

AF:

0.00

AC:

AN:

1050

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5160

East Asian (EAS)

AF:

0.00

AC:

AN:

3638

South Asian (SAS)

AF:

0.00

AC:

AN:

16476

European-Finnish (FIN)

AF:

0.00

AC:

AN:

278

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1622

European-Non Finnish (NFE)

AF:

0.00000131

AC:

AN:

762252

Other (OTH)

AF:

0.00

AC:

AN:

27312

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.4

(source)

DANN

Benign

0.75

PhyloP100

-0.21

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over