Genetic Variant TCF19:p.Pro208Ser (chr6-31161830-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007109.3(TCF19):c.622C>T(p.Pro208Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TCF19
NM_007109.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.240

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07725939).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
TCF19	NM_007109.3	MANE Select	c.622C>T	p.Pro208Ser	missense	Exon 3 of 4	NP_009040.2	A0A1U9X8M7
TCF19	NM_001077511.2		c.622C>T	p.Pro208Ser	missense	Exon 3 of 4	NP_001070979.1	A0A1U9X8M7
TCF19	NM_001318908.2		c.622C>T	p.Pro208Ser	missense	Exon 4 of 5	NP_001305837.1	Q9Y242

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCF19	ENST00000376257.8	TSL:1 MANE Select	c.622C>T	p.Pro208Ser	missense	Exon 3 of 4	ENSP00000365433.3	Q9Y242
TCF19	ENST00000376255.4	TSL:1	c.622C>T	p.Pro208Ser	missense	Exon 3 of 4	ENSP00000365431.4	Q9Y242
TCF19	ENST00000706778.1		c.622C>T	p.Pro208Ser	missense	Exon 4 of 5	ENSP00000516543.1	Q9Y242

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460558

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726620

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52288

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111892

Other (OTH)

AF:

0.00

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

4.9

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0064

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.59

M_CAP

Benign

0.0032

MetaRNN

Benign

0.077

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.5

PhyloP100

-0.24

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.72

REVEL

Benign

0.037

Sift

Benign

0.049

Sift4G

Benign

0.12

Polyphen

0.0010

Vest4

0.054

MutPred

0.19

Loss of catalytic residue at P207 (P = 0.0116)

MVP

0.28

MPC

0.55

ClinPred

0.046

GERP RS

-1.5

PromoterAI

0.11

Neutral

(source)

Varity_R

0.021

gMVP

0.35

Mutation Taster

=97/3

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over