Variant rs7750641 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000376257.8(TCF19):c.325C>T(p.Pro109Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,568,924 control chromosomes in the GnomAD database, including 13,139 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.074 ( 624 hom., cov: 33)

Exomes 𝑓: 0.12 ( 12515 hom. )

Consequence

TCF19
ENST00000376257.8 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.183

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012408197).

BP6

Variant 6-31161533-C-T is Benign according to our data. Variant chr6-31161533-C-T is described in ClinVar as [Benign]. Clinvar id is 1280459.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF19	NM_007109.3 linkuse as main transcript	c.325C>T	p.Pro109Ser	missense_variant	3/4	ENST00000376257.8	NP_009040.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF19	ENST00000376257.8 linkuse as main transcript	c.325C>T	p.Pro109Ser	missense_variant	3/4	1	NM_007109.3	ENSP00000365433	P1

Frequencies

GnomAD3 genomes

AF:

0.0742

AC:

11285

AN:

152170

Hom.:

624

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0275

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.0375

Gnomad ASJ

AF:

0.0476

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0744

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.0556

GnomAD3 exomes

AF:

0.0701

AC:

14472

AN:

206418

Hom.:

879

AF XY:

0.0689

AC XY:

7787

AN XY:

113074

show subpopulations

Gnomad AFR exome

AF:

0.0266

Gnomad AMR exome

AF:

0.0283

Gnomad ASJ exome

AF:

0.0465

Gnomad EAS exome

AF:

0.0000649

Gnomad SAS exome

AF:

0.000260

Gnomad FIN exome

AF:

0.0750

Gnomad NFE exome

AF:

0.116

Gnomad OTH exome

AF:

0.0731

GnomAD4 exome

AF:

0.119

AC:

169016

AN:

1416636

Hom.:

12515

Cov.:

AF XY:

0.115

AC XY:

81102

AN XY:

702858

show subpopulations

Gnomad4 AFR exome

AF:

0.0264

Gnomad4 AMR exome

AF:

0.0303

Gnomad4 ASJ exome

AF:

0.0482

Gnomad4 EAS exome

AF:

0.000104

Gnomad4 SAS exome

AF:

0.000381

Gnomad4 FIN exome

AF:

0.0778

Gnomad4 NFE exome

AF:

0.142

Gnomad4 OTH exome

AF:

0.105

GnomAD4 genome

AF:

0.0741

AC:

11286

AN:

152288

Hom.:

624

Cov.:

AF XY:

0.0684

AC XY:

5090

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0275

Gnomad4 AMR

AF:

0.0374

Gnomad4 ASJ

AF:

0.0476

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0744

Gnomad4 NFE

AF:

0.123

Gnomad4 OTH

AF:

0.0550

Alfa

AF:

0.106

Hom.:

2040

Bravo

AF:

0.0699

TwinsUK

AF:

0.157

AC:

581

ALSPAC

AF:

0.154

AC:

593

ESP6500AA

AF:

0.0291

AC:

ESP6500EA

AF:

0.118

AC:

592

ExAC

AF:

0.0659

AC:

7652

Asia WGS

AF:

0.00636

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 30, 2020

This variant is associated with the following publications: (PMID: 20662065, 23055271) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0021

T;T;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.51

.;T;T

MetaRNN

Benign

0.0012

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

2.0

M;M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

0.10

N;N;N

REVEL

Benign

0.038

Sift

Benign

0.27

T;T;T

Sift4G

Benign

0.32

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.039

MPC

0.54

ClinPred

0.0036

GERP RS

-1.2

Varity_R

0.045

gMVP

0.17

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over